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Inhibitors Targeting the F-BOX Proteins

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Abstract

F-box proteins are involved in multiple cellular processes through ubiquitylation and consequent degradation of targeted substrates. Any significant mutation in F-box protein-mediated proteolysis can cause human malformations. The various cellular processes F-box proteins involved include cell proliferation, apoptosis, invasion, angiogenesis, and metastasis. To target F-box proteins and their associated signaling pathways for cancer treatment, researchers have developed thousands of F-box inhibitors. The most advanced inhibitor of FBW7, NVD-BK M120, is a powerful P13 kinase inhibitor that has been proven to bring about apoptosis in cancerous human lung cells by disrupting levels of the protein known as MCL1. Moreover, F-box Inhibitors have demonstrated their efficacy for treating certain cancers through targeting particular mutated proteins. This paper explores the key studies on how F-box proteins act and their contribution to malignancy development, which fabricates an in-depth perception of inhibitors targeting the F-box proteins and their signaling pathways that eventually isolate the most promising approach to anti-cancer treatments.

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References

  1. Bai, C., et al. (1996). SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell, 86(2), 263–274.

    CAS  PubMed  Google Scholar 

  2. Wang, Z., et al. (2014). Roles of F-box proteins in cancer. Nature Reviews Cancer, 14(4), 233–247.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Kipreos, E. T., & Pagano, M. J. G. B. (2000). The F-box protein family. Genome Biology, 1, 1–7.

    Google Scholar 

  4. D’Angiolella, V., et al. (2010). SCF Cyclin F controls centrosome homeostasis and mitotic fidelity through CP110 degradation. Nature, 466(7302), 138–142.

    PubMed  PubMed Central  Google Scholar 

  5. Duan, S., et al. (2012). FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas. Nature, 481(7379), 90–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Rye, M., et al. (2011). FBXO11, a regulator of the TGF β pathway, is associated with severe otitis media in Western Australian children. Genes & Immunity, 12(5), 352–359.

    CAS  Google Scholar 

  7. Santra, M. K., Wajapeyee, N., & Green, M. R. (2009). F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature, 459(7247), 722–725.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Skaar, J. R., Pagan, J. K., & Pagano, M. (2013). Mechanisms and function of substrate recruitment by F-box proteins. Nature Reviews Molecular cell biology, 14(6), 369–381.

    CAS  PubMed  Google Scholar 

  9. Frescas, D., & Pagano, M. J. N. R. C. (2008). Deregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancer. Nature Reviews Cancer, 8(6), 438–449.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Lau, A. W., et al. (2014). The role of FBXW subfamily of F-box proteins in tumorigenesis. 15–45.

  11. Nash, P., et al. (2001). Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature, 414(6863), 514–521.

    CAS  PubMed  Google Scholar 

  12. Orlicky, S., et al. (2003). Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase. Cell, 112(2), 243–256.

    CAS  PubMed  Google Scholar 

  13. Lau, A. W., et al. The role of FBXW subfamily of F-box proteins in tumorigenesis, in SCF and APC E3 Ubiquitin Ligases in Tumorigenesis. 2014, Springer. p. 15–45.

  14. Busino, L., et al. (2003). Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage. Nature, 426(6962), 87–91.

    CAS  PubMed  Google Scholar 

  15. Jin, J., et al. (2003). SCFβ-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes & Development, 17(24), 3062–3074.

    CAS  Google Scholar 

  16. Watanabe, N., et al. (2004). M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFβ-TrCP. Proceedings of the National Academy of Sciences, 101(13), 4419–4424.

    CAS  Google Scholar 

  17. Wei, S., et al. (2008). A novel mechanism by which thiazolidinediones facilitate the proteasomal degradation of cyclin D1 in cancer cells. Journal of Biological Chemistry, 283(39), 26759–26770.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Sasajima, H., et al. (2012). Polyubiquitination of the B-cell translocation gene 1 and 2 proteins is promoted by the SCF ubiquitin ligase complex containing βTrCP. Biological and Pharmaceutical Bulletin, 35(9), 1539–1545.

    CAS  PubMed  Google Scholar 

  19. Wojcik, E. J., Glover, D. M., & Hays, T. S. (2000). The SCF ubiquitin ligase protein slimb regulates centrosome duplication in Drosophila. Current Biology, 10(18), 1131–1134.

    CAS  PubMed  Google Scholar 

  20. Zhou, B. P., et al. (2004). Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial–mesenchymal transition. Nature Cell Biology, 6(10), 931–940.

    CAS  PubMed  Google Scholar 

  21. Ray, D., Osmundson, E. C., & Kiyokawa, H. (2006). Constitutive and UV-induced fibronectin degradation is a ubiquitination-dependent process controlled by β-TrCP. Journal of Biological Chemistry, 281(32), 23060–23065.

    CAS  PubMed  Google Scholar 

  22. Ding, Q., et al. (2007). Degradation of Mcl-1 by β-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Molecular and Cellular Biology, 27(11), 4006–4017.

    CAS  PubMed  Google Scholar 

  23. Dehan, E., et al. (2009). βTrCP-and Rsk1/2-mediated degradation of BimEL inhibits apoptosis. Molecular Cell, 33(1), 109–116.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Tan, M., et al. (2006). SAG/ROC-SCFβ-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection. Neoplasia, 8(12), 1042–1054.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang, Z., et al. (2012). Skp2: a novel potential therapeutic target for prostate cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1825(1), 11–17.

    CAS  PubMed  Google Scholar 

  26. Hao, B., et al. (2005) Structural basis of the Cks1-dependent recognition of p27Kip1 by the SCFSkp2 ubiquitin ligase. 20(1): 9–19.

  27. Kamura, T., et al. (2003). Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation. Proceedings of the National Academy of Sciences, 100(18), 10231–10236.

    CAS  Google Scholar 

  28. Yu, Z.-K., Gervais, J. L., & Zhang, H. (1998). Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21CIP1/WAF1 and cyclin D proteins. Proceedings of the National Academy of Sciences, 95(19), 11324–11329.

    CAS  Google Scholar 

  29. Tedesco, D., Lukas, J., & Reed, S. I. (2002). The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein–ubiquitin ligase SCFSkp2. Genes & Development, 16(22), 2946–2957.

    CAS  Google Scholar 

  30. Hiramatsu, Y., et al. (2006). Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination. Cancer Research, 66(17), 8477–8483.

    CAS  PubMed  Google Scholar 

  31. Huang, H., et al. (2005). Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proceedings of the National Academy of Sciences, 102(5), 1649–1654.

    CAS  Google Scholar 

  32. Seki, R., et al. (2003). Prognostic significance of the F‐box protein Skp2 expression in diffuse large B‐cell lymphoma. American journal of Hematology, 73(4), 230–235.

    PubMed  Google Scholar 

  33. Wang, H., et al. (2010). Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/− mice. Nature Genetics, 42(1), 83.

    CAS  PubMed  Google Scholar 

  34. Li, J.-Q., et al. (2004). Correlation of Skp2 with carcinogenesis, invasion, metastasis, and prognosis in colorectal tumors. International Journal of Oncology, 25(1), 87–95.

    PubMed  Google Scholar 

  35. Rose, A. E., et al. (2011). Clinical relevance of SKP2 alterations in metastatic melanoma. Pigment Cell & Melanoma Research, 24(1), 197–206.

    CAS  Google Scholar 

  36. Fang, F.-M., et al. (2009). Effect of S-phase kinase-associated protein 2 expression on distant metastasis and survival in nasopharyngeal carcinoma patients. International Journal of Radiation Oncology* Biology* Physics, 73(1), 202–207.

    CAS  PubMed  Google Scholar 

  37. Schüler, S., et al. (2011). SKP2 confers resistance of pancreatic cancer cells towards TRAIL-induced apoptosis. International Journal of Oncology, 38(1), 219–225.

    PubMed  Google Scholar 

  38. Radke, S., Pirkmaier, A., & Germain, D. (2005). Differential expression of the F-box proteins Skp2 and Skp2B in breast cancer. Oncogene, 24(21), 3448–3458.

    CAS  PubMed  Google Scholar 

  39. Ma, X.-M., et al. (2005). Relation of overexpression of S phase kinase-associated protein 2 with reduced expression of p27 and PTEN in human gastric carcinoma. World Journal of Gastroenterology: WJG, 11(42), 6716.

    PubMed  PubMed Central  Google Scholar 

  40. Wang, Z., et al. (2012). Skp2 is a promising therapeutic target in breast cancer. Frontiers in Oncology, 1, 57.

    PubMed  PubMed Central  Google Scholar 

  41. Kitagawa, M., Lee, S. H., & McCormick F. (2007). Skp2 suppresses p53-dependent apoptosis by inhibiting p300-mediated trans-activation. AACR.

  42. Wu, L., et al. (2012). Specific small molecule inhibitors of Skp2-mediated p27 degradation. Chemistry & Biology, 19(12), 1515–1524.

    CAS  Google Scholar 

  43. Nakayama, K., et al. (2004). Skp2-mediated degradation of p27 regulates progression into mitosis. Developmental Cell, 6(5), 661–672.

    CAS  PubMed  Google Scholar 

  44. Chan, C.-H., et al. (2012). The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis. Cell, 149(5), 1098–1111.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Hershko, D. D. (2008). Oncogenic properties and prognostic implications of the ubiquitin ligase Skp2 in cancer. Cancer, 112(7), 1415–1424.

    CAS  PubMed  Google Scholar 

  46. Lin, H.-K., et al. (2009). Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB. Nature Cell Biology, 11(4), 420–432.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Lin, H.-K., et al. (2010). Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature, 464(7287), 374–379.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhang, S., (2011). Computer-aided drug discovery and development. Drug Design and Discovery 23–38.

  49. Chan, C.-H., et al. (2013). Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell, 154(3), 556–568.

    CAS  PubMed  Google Scholar 

  50. Zheng, X.-Y., et al. (2004). Correlation of Skp2 and P27kip1 protein expression and clinicopathological features of prostate cancer. Ai zheng= Aizheng= Chinese Journal of Cancer, 23(2), 215–218.

    CAS  PubMed  Google Scholar 

  51. Schulman, B. A., et al. (2000). Insights into SCF ubiquitin ligases from the structure of the Skp1–Skp2 complex. Nature, 408(6810), 381–386.

    CAS  PubMed  Google Scholar 

  52. Zheng, N., et al. (2002). Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex. Nature, 416(6882), 703–709.

    CAS  PubMed  Google Scholar 

  53. Wen, Y., Wang, K., & Yang, K. (2016). Inhibiting the role of Skp2 suppresses cell proliferation and tumorigenesis of human gastric cancer cells via the upregulation of p27kip1. Molecular Medicine Reports, 14(4), 3917–3924.

    CAS  PubMed  Google Scholar 

  54. Lin, S.-X., et al. (2010). Molecular therapy of breast cancer: progress and future directions. Nature Reviews Endocrinology, 6(9), 485–493.

    CAS  PubMed  Google Scholar 

  55. Lu, Y., Zi, X., & Pollak, M. (2004). Molecular mechanisms underlying IGF‐I‐induced attenuation of the growth‐inhibitory activity of trastuzumab (Herceptin) on SKBR3 breast cancer cells. International Journal of Cancer, 108(3), 334–341.

    CAS  PubMed  Google Scholar 

  56. Frankland-Searby, S., & Bhaumik, S. R. (2012). The 26S proteasome complex: an attractive target for cancer therapy. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1825(1), 64–76.

    CAS  PubMed  Google Scholar 

  57. Uddin, S., et al. (2008). Bortezomib (Velcade) induces p27Kip1 expression through S-phase kinase protein 2 degradation in colorectal cancer. Cancer Research, 68(9), 3379–3388.

    CAS  PubMed  Google Scholar 

  58. Mackay, H., et al. (2005). A phase II trial with pharmacodynamic endpoints of the proteasome inhibitor bortezomib in patients with metastatic colorectal cancer. Clinical Cancer Research, 11(15), 5526–5533.

    CAS  PubMed  Google Scholar 

  59. Park, E.-J., et al. (2013). Suppression of Src/ERK and GSK-3/β-catenin signaling by pinosylvin inhibits the growth of human colorectal cancer cells. Food and Chemical Toxicology, 55, 424–433.

    CAS  PubMed  Google Scholar 

  60. Voutsadakis, I. A. (2008). The ubiquitin-proteasome system in colorectal cancer. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1782(12), 800–808.

    CAS  PubMed  Google Scholar 

  61. Chen, Q., et al. 441 Krenitsky VP, Xu W, Moutouh-de Parseval L, Webb DR, Mercurio F, Nakayama 442 KI, Nakayama K, Orlowski RZ. Targeting the p27 E3 ligase SCF (Skp2) results in p27-443 and Skp2-mediated cell-cycle arrest and activation of autophagy. Blood. 111, 4690–4699.

  62. Bochis, O. V., et al. (2015). The role of Skp2 and its substrate CDKN1B (p27) in colorectal cancer. Journal of Gastrointestinal & Liver Diseases, 24(2), 225–234.

    Google Scholar 

  63. Liao, Y., et al. (2014). Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells. Cell Death & Disease, 5(3), e1137–e1137.

    CAS  Google Scholar 

  64. Su, J., et al. (2016). Curcumin inhibits cell growth and invasion and induces apoptosis through down-regulation of Skp2 in pancreatic cancer cells. American Journal of Cancer Research, 6(9), 1949.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Huang, H.-C., Lin, C.-L., & Lin, J.-K. (2011). 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose, quercetin, curcumin and lycopene induce cell-cycle arrest in MDA-MB-231 and BT474 cells through downregulation of Skp2 protein. Journal of Agricultural and Food Chemistry, 59(12), 6765–6775.

    CAS  PubMed  Google Scholar 

  66. Li, X., et al. (2015). Flavokawain A induces deNEDDylation and Skp2 degradation leading to inhibition of tumorigenesis and cancer progression in the TRAMP transgenic mouse model. Oncotarget, 6(39), 41809.

    PubMed  PubMed Central  Google Scholar 

  67. Jiang, W., Lin, M., & Wang, Z. (2020). Dioscin: A new potential inhibitor of Skp2 for cancer therapy. EBioMedicine, 51, 102593.

    PubMed  PubMed Central  Google Scholar 

  68. Lee, H., et al. (2006). Mouse emi1 has an essential function in mitotic progression during early embryogenesis. Molecular and Cellular Biology, 26(14), 5373–5381.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Min, K.-W., et al. (2013). Clear cell carcinomas of the ovary: a multi-institutional study of 129 cases in Korea with prognostic significance of Emi1 and Galectin-3. International Journal Gynecological Pathology, 32(1), 3–14.

    CAS  Google Scholar 

  70. Lehman, N. L., et al. (2007). Oncogenic regulators and substrates of the anaphase promoting complex/cyclosome are frequently overexpressed in malignant tumors. American Journal Pathology, 170(5), 1793–1805.

    CAS  Google Scholar 

  71. Visintin, R., Prinz, S., & Amon, A. (1997). CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science, 278(5337), 460–463.

    CAS  PubMed  Google Scholar 

  72. Sivakumar, S., & Gorbsky, G. J. (2015). Spatiotemporal regulation of the anaphase-promoting complex in mitosis. Nature Reviews Molecular Cell Biology, 16(2), 82–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Rahimi, H., et al. (2015). The expression pattern of APC2 and APC7 in various cancer cell lines and AML patients. Advances in Medical Sciences, 60(2), 259–263.

    PubMed  Google Scholar 

  74. VanGenderen, C., Harkness, T. A. A., & Arnason, T. G. (2020). The role of Anaphase Promoting Complex activation, inhibition and substrates in cancer development and progression. Aging (Albany NY), 12(15), 15818.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Machida, Y. J., & Dutta, A. (2007). The APC/C inhibitor, Emi1, is essential for prevention of rereplication. Genes & Development, 21(2), 184–194.

    CAS  Google Scholar 

  76. Sailo, B. L., et al. (2019). FBXW7 in cancer: what has been unraveled thus far? Cancers, 11(2), 246.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Tu, K., et al. (2013). Recombinant human adenovirus-p53 injection induced apoptosis in hepatocellular carcinoma cell lines mediated by p53-Fbxw7 pathway, which controls c-Myc and cyclin E. PloS One, 8(7), e68574.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Sato, M., et al. (2015). MYC is a critical target of FBXW7. Oncotarget, 6(5), 3292.

    PubMed  Google Scholar 

  79. Wei, W., et al. (2005). The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell, 8(1), 25–33.

    CAS  PubMed  Google Scholar 

  80. Sancho, R., et al. (2013). Fbw7 repression by hes5 creates a feedback loop that modulates Notch-mediated intestinal and neural stem cell fate decisions. PLoS Biology, 11(6), e1001586.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Yokobori, T., et al. (2014). FBXW7 mediates chemotherapeutic sensitivity and prognosis in NSCLCs. Molecular Cancer Research, 12(1), 32–37.

    CAS  PubMed  Google Scholar 

  82. Ren, H., et al. (2013). The PI3 kinase inhibitor NVP-BKM120 induces GSK3/FBXW7-dependent Mcl-1 degradation, contributing to induction of apoptosis and enhancement of TRAIL-induced apoptosis. Cancer Letters, 338(2), 229–238.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Welcker, M., & Clurman, B. E. (2007). Fbw7/hCDC4 dimerization regulates its substrate interactions. Cell Division, 2(1), 1–13.

    Google Scholar 

  84. Tang, X., et al. (2007). Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination. Cell, 129(6), 1165–1176.

    CAS  PubMed  Google Scholar 

  85. Flugel, D., Gorlach, A., & Kietzmann T. (2011). Glycogen synthase kinase-3beta regulates cell growth, migration and angiogenesis via Fbw7 and USP-28-dependent degradation of hypoxia-inducible factor-1alpha. Blood.

  86. Cao, J., Ge, M.-H., & Ling Z.-Q. (2016). Fbxw7 tumor suppressor: a vital regulator contributes to human tumorigenesis. Medicine. 95(7).

  87. Isobe, T., et al. (2009). Adenovirus E1A inhibits SCFFbw7 ubiquitin ligase. Journal of Biological Chemistry, 284(41), 27766–27779.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Mao, J.-H., et al. (2004). Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature, 432(7018), 775–779.

    CAS  PubMed  Google Scholar 

  89. Calcagno, D. Q., et al. (2013). MYC, FBXW7 and TP53 copy number variation and expression in gastric cancer. BMC Gastroenterology, 13(1), 1–10.

    Google Scholar 

  90. Kimura, T., et al. (2003). hCDC4b, a regulator of cyclin E, as a direct transcriptional target of p53. Cancer Science, 94(5), 431–436.

    CAS  PubMed  Google Scholar 

  91. Li, Z., et al. (2015). p53 mutation directs AURKA overexpression via miR-25 and FBXW7 in prostatic small cell neuroendocrine carcinoma. Molecular Cancer Research, 13(3), 584–591.

    CAS  PubMed  Google Scholar 

  92. Balamurugan, K., & Sterneck, E. (2013). The many faces of C/EBPδ and their relevance for inflammation and cancer. International Journal of Biological Sciences, 9(9), 917.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Gery, S., et al. (2005). C/EBPδ expression in a BCR-ABL-positive cell line induces growth arrest and myeloid differentiation. Oncogene, 24(9), 1589–1597.

    CAS  PubMed  Google Scholar 

  94. Welcker, M., & Clurman, B. E. (2008). FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nature Reviews Cancer, 8(2), 83–93.

    CAS  PubMed  Google Scholar 

  95. Lu, K. P., & Zhou, X. Z. (2007). The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease. Nature Reviews Molecular Cell Biology, 8(11), 904–916.

    CAS  PubMed  Google Scholar 

  96. Min, S.-H., et al. (2012). Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase. Molecular Cell, 46(6), 771–783.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Wang, L., et al. (2014). Aberrant regulation of FBW7 in cancer. Oncotarget, 5(8), 2000.

    PubMed  PubMed Central  Google Scholar 

  98. Jiang, X., et al. (2012). Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity. Stem Cells, 30(7), 1313–1326.

    CAS  PubMed  Google Scholar 

  99. Wang, Q., et al. (2011). Upregulation of miR-27a contributes to the malignant transformation of human bronchial epithelial cells induced by SV40 small T antigen. Oncogene, 30(36), 3875–3886.

    CAS  PubMed  Google Scholar 

  100. Lerner, M., et al. (2011). MiRNA-27a controls FBW7/hCDC4-dependent cyclin E degradation and cell cycle progression. Cell Cycle, 10(13), 2172–2183.

    CAS  PubMed  Google Scholar 

  101. Panka, D. J., et al. (2008). GSK-3β inhibition enhances sorafenib-induced apoptosis in melanoma cell lines. Journal Biological Chemistry, 283(2), 726–732.

    CAS  Google Scholar 

  102. Konopleva, M., et al. (2008). Mechanisms of antileukemic activity of the novel Bcl-2 homology domain-3 mimetic GX15-070 (obatoclax). Cancer Research, 68(9), 3413–3420.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Cragg, M. S., et al. (2009). Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics. Nature Reviews Cancer, 9(5), 321–326.

    CAS  PubMed  Google Scholar 

  104. Nijhawan, D., et al. (2003). Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes & Development, 17(12), 1475–1486.

    CAS  Google Scholar 

  105. Liu, Y., & Mallampalli, R. K. Small molecule therapeutics targeting F-box proteins in cancer. in Seminars in Cancer Biology. 2016. Elsevier.

  106. Yan, L., et al. (2020). Emerging roles of F-box proteins in cancer drug resistance. Drug Resistance Updates, 49, 100673.

    PubMed  Google Scholar 

  107. Xiao, Y., et al. (2018). FBXW 7 deletion contributes to lung tumor development and confers resistance to gefitinib therapy. Molecular Oncology, 12(6), 883–895.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Feng, C., Yang, F., & Wang, J. (2017). FBXO4 inhibits lung cancer cell survival by targeting Mcl-1 for degradation. Cancer Gene Therapy, 24(8), 342–347.

    CAS  PubMed  Google Scholar 

  109. Kang, J.-H., et al. (2017). Regulation of FBXO4-mediated ICAM-1 protein stability in metastatic breast cancer. Oncotarget, 8(47), 83100.

    PubMed  PubMed Central  Google Scholar 

  110. Qie, S., et al. (2019). Targeting glutamine-addiction and overcoming CDK4/6 inhibitor resistance in human esophageal squamous cell carcinoma. Nature Communications, 10(1), 1–15.

    CAS  Google Scholar 

  111. Lian, Z., et al. (2015). FBXO4 loss facilitates carcinogen induced papilloma development in mice. Cancer Biology & Therapy, 16(5), 750–755.

    CAS  Google Scholar 

  112. Yoshida, A., et al. (2019). SLC36A1-mTORC1 signaling drives acquired resistance to CDK4/6 inhibitors. Science Advances, 5(9), eaax6352.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Tekcham, D. S., et al. (2020). F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects. Theranostics, 10(9), 4150.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Shima, Y., et al. (2008). PML activates transcription by protecting HIPK2 and p300 from SCFFbx3-mediated degradation. Molecular and Cellular Biology, 28(23), 7126–7138.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Chen, B. B., et al. (2013). A combinatorial F box protein directed pathway controls TRAF adaptor stability to regulate inflammation. Nature Immunology, 14(5), 470–479.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Shao, W., et al. (2016). FBXO3 protein promotes ubiquitylation and transcriptional activity of AIRE (autoimmune regulator). Journal of Biological Chemistry, 291(34), 17953–17963.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Li, D., et al. (2015). F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Biochemical and Biophysical Research Communications, 458(4), 941–945.

    CAS  PubMed  Google Scholar 

  118. Kogure, N., et al. (2017). Low expression of FBXO45 is associated with gastric cancer progression and poor prognosis. Anticancer Research, 37(1), 191–196.

    CAS  PubMed  Google Scholar 

  119. Siepka, S. M., et al. (2007). Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression. Cell, 129(5), 1011–1023.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Yamanaka, I., et al. (2007). Presence of robust circadian clock oscillation under constitutive over-expression of mCry1 in rat-1 fibroblasts. FEBS Letters, 581(21), 4098–4102.

    CAS  PubMed  Google Scholar 

  121. Godinho, S. I., et al. (2007). The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period. Science, 316(5826), 897–900.

    CAS  PubMed  Google Scholar 

  122. Busino, L., et al. (2007). SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science, 316(5826), 900–904.

    CAS  PubMed  Google Scholar 

  123. Huber, A.-L., et al. (2016). CRY2 and FBXL3 cooperatively degrade c-MYC. Molecular Cell, 64(4), 774–789.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Correia, S. P., et al. (2019). The circadian E3 ligase complex SCF FBXL3+ CRY targets TLK2. Scientific Reports, 9(1), 1–9.

    CAS  Google Scholar 

  125. Fuchs, S. Y., Spiegelman, V. S., & Kumar, K. S. (2004). The many faces of β-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer. Oncogene, 23(11), 2028–2036.

    CAS  PubMed  Google Scholar 

  126. Margottin-Goguet, F., et al. (2003). Prophase destruction of Emi1 by the SCFβTrCP/Slimb ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Developmental Cell, 4(6), 813–826.

    CAS  PubMed  Google Scholar 

  127. Wei, X., et al. (2018). SKP2 promotes hepatocellular carcinoma progression through nuclear AMPK-SKP2-CARM1 signaling transcriptionally regulating nutrient-deprived autophagy induction. Cellular Physiology and Biochemistry, 47(6), 2484–2497.

    CAS  PubMed  Google Scholar 

  128. Dorrello, N. V., et al. (2006). S6K1-and ßTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science, 314(5798), 467–471.

    CAS  PubMed  Google Scholar 

  129. Perkins, N. D. (2007). Integrating cell-signalling pathways with NF-κB and IKK function. Nature Reviews Molecular Cell Biology, 8(1), 49–62.

    CAS  PubMed  Google Scholar 

  130. Chen, Z. J. (2005). Ubiquitin signalling in the NF-κB pathway. Nature Cell Biology, 7(8), 758–765.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Yaron, A., et al. (1998). Identification of the receptor component of the IκBα–ubiquitin ligase. Nature, 396(6711), 590–594.

    CAS  PubMed  Google Scholar 

  132. Nakajima, H., et al. (2008). A novel small-molecule inhibitor of NF-κB signaling. Biochemical and Biophysical Research Communications, 368(4), 1007–1013.

    CAS  PubMed  Google Scholar 

  133. Nakayama, K., et al. (2003). Impaired degradation of inhibitory subunit of NF-κB (IκB) and β-catenin as a result of targeted disruption of the β-TrCP1 gene. Proceedings of the National Academy of Sciences, 100(15), 8752–8757.

    CAS  Google Scholar 

  134. Yang, H.-S., et al. (2003). The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. Molecular and Cellular Biology, 23(1), 26–37.

    PubMed  PubMed Central  Google Scholar 

  135. Blees, J. S., et al. (2012). Erioflorin stabilizes the tumor suppressor Pdcd4 by inhibiting its interaction with the E3-ligase β-TrCP1. PloS one, 7(10), e46567.

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Peterson, T. R., et al. (2009). DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell, 137(5), 873–886.

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Duan, S., et al. (2011). mTOR generates an auto-amplification loop by triggering the βTrCP-and CK1α-dependent degradation of DEPTOR. Molecular cell, 44(2), 317–324.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Wang, Z., et al. (2012). DEPTOR ubiquitination and destruction by SCFβ-TrCP. American Journal of Physiology-Endocrinology and Metabolism, 303(2), E163–E169.

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Zhao, Y., Xiong, X., & Sun, Y. (2011). DEPTOR, an mTOR inhibitor, is a physiological substrate of SCFβTrCP E3 ubiquitin ligase and regulates survival and autophagy. Molecular Cell, 44(2), 304–316.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Sakamoto, K. M., et al. (2001). Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation. Proceedings of the National Academy of Sciences, 98(15), 8554–8559.

    CAS  Google Scholar 

  141. Sakamoto, K. M., et al. (2003). Development of Protacs to target cancer-promoting proteins for ubiquitination and degradation. Molecular & Cellular Proteomics, 2(12), 1350–1358.

    CAS  Google Scholar 

  142. Schneekloth, A. R., et al. (2008). Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics. Bioorganic & Medicinal Chemistry Letters, 18(22), 5904–5908.

    CAS  Google Scholar 

  143. O’Connor, L., et al. (1998). Bim: a novel member of the Bcl‐2 family that promotes apoptosis. The EMBO Journal, 17(2), 384–395.

    PubMed  PubMed Central  Google Scholar 

  144. Fletcher, J. I., & Huang, D. C. (2008). Controlling the cell death mediators Bax and Bak: puzzles and conundrums. Cell Cycle, 7(1), 39–44.

    CAS  PubMed  Google Scholar 

  145. Rogers, G. C., et al. (2009). The SCFSlimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. Journal of Cell Biology, 184(2), 225–239.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Cunha-Ferreira, I., et al. (2009). The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4. Current Biology, 19(1), 43–49.

    CAS  PubMed  Google Scholar 

  147. Bornstein, G., et al. (2003). Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase. Journal of Biological Chemistry, 278(28), 25752–25757.

    CAS  PubMed  Google Scholar 

  148. Carrano, A. C., et al. (1999). SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nature Cell Biology, 1(4), 193–199.

    CAS  PubMed  Google Scholar 

  149. Bhattacharya, S., et al. (2003). SKP2 associates with p130 and accelerates p130 ubiquitylation and degradation in human cells. Oncogene, 22(16), 2443–2451.

    CAS  PubMed  Google Scholar 

  150. Yeh, K.-H., et al. (2001). The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E. Biochemical and Biophysical Research Communications, 281(4), 884–890.

    CAS  PubMed  Google Scholar 

  151. Von Der Lehr, N., et al. (2003). The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. Molecular Cell, 11(5), 1189–1200.

    PubMed  Google Scholar 

  152. Yao, F., et al. (2018). SKP2-and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity. Nature Communications, 9(1), 1–16.

    Google Scholar 

  153. Clement, E., et al. (2018). Skp2-dependent reactivation of AKT drives resistance to PI3K inhibitors. Science Signaling, 11(521), eaao3810.

    PubMed  PubMed Central  Google Scholar 

  154. Strohmaier, H., et al. (2001). Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature, 413(6853), 316–322.

    CAS  PubMed  Google Scholar 

  155. Mao, J.-H., et al. (2008). FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science, 321(5895), 1499–1502.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Close, V., et al. (2019). FBXW7 mutations reduce binding of NOTCH1, leading to cleaved NOTCH1 accumulation and target gene activation in CLL. Blood, The Journal of the American Society of Hematology, 133(8), 830–839.

    CAS  Google Scholar 

  157. Pine, S. R. (2018). Rethinking Gamma-secretase Inhibitors for Treatment of Non–small-Cell Lung Cancer: Is Notch the Target? Rethinking Gamma Secretase Inhibitors. Clinical Cancer Research, 24(24), 6136–6141.

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Gao, J., et al. (2014). Nuclear retention of Fbw7 by specific inhibitors of nuclear export leads to Notch1 degradation in pancreatic cancer. Oncotarget, 5(11), 3444.

    PubMed  PubMed Central  Google Scholar 

  159. Babaei-Jadidi, R., et al. (2011). FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation. Journal of Experimental Medicine, 208(2), 295–312.

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Zhang, Z. & Richmond A. (2021). The role of PI3K inhibition in the treatment of breast cancer, alone or combined with immune checkpoint inhibitors. Frontiers in Molecular Biosciences, 286.

  161. Su, S., et al. (2022). PLK1 inhibition-based combination therapies for cancer management. Translational Oncology, 16, 101332.

    CAS  PubMed  Google Scholar 

  162. Gutteridge, R. E. A., et al. (2016). Plk1 inhibitors in cancer therapy: from laboratory to clinics. Molecular Cancer Therapeutics, 15(7), 1427–1435.

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Mori, A., et al. (2018). FBXW 7 modulates malignant potential and cisplatin‐induced apoptosis in cholangiocarcinoma through NOTCH 1 and MCL 1. Cancer Science, 109(12), 3883–3895.

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Yada, M., et al. (2004). Phosphorylation‐dependent degradation of c‐Myc is mediated by the F‐box protein Fbw7. The. EMBO Journal, 23(10), 2116–2125.

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Gergely, P. A., et al. (2019). Tyrosine kinase inhibitor imatinib mesylate alters DMBA-induced early onco/suppressor gene expression with tissue-specificity in mice. BioMed Research International, 2019, 8670398.

  166. Suenaga, M., et al. (2013). Influence of gefitinib and erlotinib on apoptosis and C-MYC expression in H23 lung cancer cells. Anticancer Research, 33(4), 1547–1554.

    CAS  PubMed  Google Scholar 

  167. Lee, E. K., et al. (2013). The FBXO4 tumor suppressor functions as a barrier to BRAFV600E-dependent metastatic melanoma. Molecular and Cellular Biology, 33(22), 4422–4433.

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Achkar, I. W., et al. (2018). Cisplatin based therapy: the role of the mitogen activated protein kinase signaling pathway. Journal of Translational Medicine, 16(1), 1–12.

    Google Scholar 

  169. Roy, S., et al. (2018). p38 MAPK pathway and its interaction with TRF2 in cisplatin induced chemotherapeutic response in head and neck cancer. Oncogenesis, 7(7), 1–16.

    Google Scholar 

  170. Liu, K., et al. (2013). Synergistic effect of paclitaxel and epigenetic agent phenethyl isothiocyanate on growth inhibition, cell cycle arrest and apoptosis in breast cancer cells. Cancer Cell International, 13(1), 1–8.

    CAS  Google Scholar 

  171. Qie, S., et al. (2017). Fbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and neck squamous cell carcinoma. Nat Commun, 8, 1534.

    PubMed  PubMed Central  Google Scholar 

  172. Wang, B., et al. (2021). circNRIP1 facilitates keloid progression via FXR1-mediated upregulation of miR-503-3p and miR-503-5p. International Journal of Molecular Medicine, 47(5), 1–13.

    PubMed  Google Scholar 

  173. Peng, J., et al. (2018). An Hsp20-FBXO4 axis regulates adipocyte function through modulating PPARγ ubiquitination. Cell Reports, 23(12), 3607–3620.

    CAS  PubMed  Google Scholar 

  174. Lin, D. I., et al. (2006). Phosphorylation-dependent ubiquitination of cyclin D1 by the SCFFBX4-αB crystallin complex. Molecular Cell, 24(3), 355–366.

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Braal, C. L., et al. (2021). Inhibiting CDK4/6 in breast cancer with palbociclib, ribociclib, and abemaciclib: similarities and differences. Drugs, 81(3), 317–331.

    CAS  PubMed  Google Scholar 

  176. Andrzejewski, S., et al. (2017). PGC-1α promotes breast cancer metastasis and confers bioenergetic flexibility against metabolic drugs. Cell Metabolism, 26(5), 778–787.e5.

    CAS  PubMed  Google Scholar 

  177. Qie, S., et al. (2019). Targeting glutamine-addiction and overcoming CDK4/6 inhibitor resistance in human esophageal squamous cell carcinoma. Nature Communications, 10(1), 1296.

    PubMed  PubMed Central  Google Scholar 

  178. D’Angiolella, V., et al. (2012). Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell, 149(5), 1023–1034.

    PubMed  PubMed Central  Google Scholar 

  179. Fu, J., et al. (2013). Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis. Cancer Science, 104(4), 508–515.

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Emanuele, M. J., et al. (2011). Global identification of modular cullin-RING ligase substrates. Cell, 147(2), 459–474.

    CAS  PubMed  PubMed Central  Google Scholar 

  181. Walter, D., et al. (2016). SCF (cyclin F)-dependent degradation of CDC6 suppresses DNA re-replication. Nat Commun, 7, 10530.

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Altomonte, J., et al. (2003). Inhibition of Foxo1 function is associated with improved fasting glycemia in diabetic mice. American Journal of Physiology Endocrinology and Metabolism, 285(4), E718–E728.

    CAS  PubMed  Google Scholar 

  183. Haeusler, R. A., Kaestner, K. H., & Accili, D. J. J. O. B. C. (2010). FoxOs function synergistically to promote glucose production. Journal of Biologcal Chemistry, 285(46), 35245–35248.

    CAS  Google Scholar 

  184. Langlet, F., et al. (2017). Selective inhibition of FOXO1 activator/repressor balance modulates hepatic glucose handling. Cell, 171(4), 824–835.e18.

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Pandey, A., et al. (2016). FoxO1 inhibitors: the future medicine for metabolic disorders? Current Diabetes Reviews, 12(3), 223–230.

    CAS  PubMed  Google Scholar 

  186. Mallampalli, R. K., et al. (2013). Targeting F box protein Fbxo3 to control cytokine-driven inflammation. Journal Immunology, 191(10), 5247–5255.

    CAS  Google Scholar 

  187. Lomonosov, M., et al. (2011). Expression of Fbxo7 in haematopoietic progenitor cells cooperates with p53 loss to promote lymphomagenesis. PLoS One, 6(6), e21165.

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Zheng, H., et al. (2014). PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis. Cancer cell, 26(3), 358–373.

    CAS  PubMed  PubMed Central  Google Scholar 

  189. Pighi, C., et al. (2021). Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma. Blood Advances, 5(23), 5239–5257.

    CAS  PubMed  PubMed Central  Google Scholar 

  190. Zou, S., et al. (2018). FBXO31 suppresses gastric cancer EMT by targeting Snail1 for proteasomal degradationubiquitination and degradation of Snail1 by FBXO31. Molecular Cancer Research, 16(2), 286–295.

    CAS  PubMed  Google Scholar 

  191. Malonia, S. K., et al. (2015). F-box protein FBXO31 directs degradation of MDM2 to facilitate p53-mediated growth arrest following genotoxic stress. Proceedings of the National Academy of Sciences, 112(28), 8632–8637.

    CAS  Google Scholar 

  192. Liu, J., et al. (2014). F-box only protein 31 (FBXO31) negatively regulates p38 mitogen-activated protein kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and degradation of mitogen-activated protein kinase kinase 6 (MKK6). Journal of Biological Chemistry, 289(31), 21508–21518.

    PubMed  PubMed Central  Google Scholar 

  193. Chung, F.-Z., et al. (2014). Fbxo45 inhibits calcium-sensitive proteolysis of N-cadherin and promotes neuronal differentiation. Journal of Biological Chemistry, 289(41), 28448–28459.

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Chen, X., et al. (2014). Fbxo45-mediated degradation of the tumor-suppressor Par-4 regulates cancer cell survival. Cell Death & Differentiation, 21(10), 1535–1545.

    CAS  Google Scholar 

  195. Peschiaroli, A., et al. (2009). The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73. Oncogene, 28(35), 3157–3166.

    CAS  PubMed  Google Scholar 

  196. English, J. M., & Cobb, M. H. J. T. I. P. S. (2002). Pharmacological inhibitors of MAPK pathways. Trends in Pharmacological Sciences, 23(1), 40–45.

    CAS  PubMed  Google Scholar 

  197. Sahasrabuddhe, A. A., et al. (2021). A novel FBXO45-Gef-H1 axis controls oncogenic signaling in B-cell lymphoma. Blood, 138(Supplement 1), 711–711.

    Google Scholar 

  198. Correia, S., et al. (2019). The circadian E3 ligase complex SCF (FBXL3+ CRY) targets TLK2. Sci Rep, 9(1), 198.

    PubMed  PubMed Central  Google Scholar 

  199. Hart, M., et al. (1999). The F-box protein β-TrCP associates with phosphorylated β-catenin and regulates its activity in the cell. Current Biology, 9(4), 207–211.

    CAS  PubMed  Google Scholar 

  200. Wei, S., et al. (2007). Thiazolidinediones modulate the expression of β-catenin and other cell-cycle regulatory proteins by targeting the F-box proteins of Skp1-Cul1-F-box protein E3 ubiquitin ligase independently of peroxisome proliferator-activated receptor γ. Molecular Pharmacology, 72(3), 725–733.

    CAS  PubMed  Google Scholar 

  201. Winston, J. T., et al. (1999). The SCFβ-TRCP–ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IκBα and β-catenin and stimulates IκBα ubiquitination in vitro. Genes & Development, 13(3), 270–283.

    CAS  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant Numbers. 31900913, 82020108030, and U21A20416), the National Key Research Program (grant number 2018YFE0195100), and the Postgraduate Education Reform Project of Zhengzhou university in 2021 (grant number YJSJY202159). This work was also supported by the Education Reform Research Project (for international students) of Zhengzhou University in 2022 (grant number 2022ZZUJGXMLXS-031), the Training Program of Innovation and Entrepreneurship for College Students (Undergraduate Research Training Program number 202310459149). Thanks to the support from the National Supercomputing Center in Zhengzhou, thanks to the support from Shanghai Synchrotron Radiation Facility and National Facility for Protein Science Shanghai(NFPSS).

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  1. These authors contributed equally: Yalnaz Naseem, Chaofeng Zhang, Jianshu Dong

Authors and Affiliations

  1. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China

    Yalnaz Naseem, Chaofeng Zhang, Xinyi Zhou, Jianshu Dong, Jiachong Xie, Huimin Zhang, Clement Agboyibor & YueFeng Bi

  2. Institute of Drug Discovery and Development, Zhengzhou University, Zhengzhou, 450001, China

    Yalnaz Naseem, Chaofeng Zhang, Xinyi Zhou, Jianshu Dong, Jiachong Xie, Huimin Zhang, Clement Agboyibor, YueFeng Bi & Hongmin Liu

  3. Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou, 450001, China

    Yalnaz Naseem, Chaofeng Zhang, Xinyi Zhou, Jianshu Dong, Jiachong Xie, Huimin Zhang, Clement Agboyibor, YueFeng Bi & Hongmin Liu

  4. Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001, China

    Yalnaz Naseem, Chaofeng Zhang, Xinyi Zhou, Jianshu Dong, Jiachong Xie, Huimin Zhang, Clement Agboyibor, YueFeng Bi & Hongmin Liu

  5. Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou University, Zhengzhou, 450001, China

    Yalnaz Naseem, Chaofeng Zhang, Xinyi Zhou, Jianshu Dong, Jiachong Xie, Huimin Zhang, Clement Agboyibor, YueFeng Bi & Hongmin Liu

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C.Z., Y.N. and J.D. contributed equally to this work.

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Naseem, Y., Zhang, C., Zhou, X. et al. Inhibitors Targeting the F-BOX Proteins. Cell Biochem Biophys 81, 577–597 (2023). https://doi.org/10.1007/s12013-023-01160-1

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