Skip to main content
Log in

The role of ubiquitin signaling pathway on liver regeneration in rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The ubiquitin signalling pathway is a large system associated with numerous intracellular mechanisms. However, its function in the liver regeneration process remains unknown. This particular study investigates the intracellular effect mechanisms of the ubiquitin signalling pathway. It also determines the differences in the expression of 88 genes belonging to the ubiquitin pathway using the RT-PCR array method. To conduct this research, three genes—that differed in the expression analysis were selected. Moreover, their proteins were analysed by western blot analysis while using Ki67 immunohistochemical analysis that determines proliferation rates by hour. It was determined that BRCA1 and BARD1, which are effective in DNA repair, play an active role at PH24. Similarly, Ube2t expression, which belongs to the Fanconi anaemia pathway associated with DNA repair, was also found to be high at PH12-72 h. In addition, it was revealed that the expressions of Anapc2, Anapc11, Cdc20 belonging to the APC/CCdc20 complex, which participate in cell cycle regulation, differed at different hours after PH. Expression of Mul1, which is involved in mitochondrial biogenesis and mitophagy mechanisms, peaked at PH12 under the observation. Considering the Mul1 gene expression difference, MUL1-mediated mitophagy and mitochondrial fission mechanism may be associated with liver regeneration. It was also determined that PARKIN-mediated mitophagy mechanisms are not active in 0–72 h of liver regeneration since PARKIN expression did not show a significant change in PH groups.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

The online version of RT-PCR Array data (unnormalized/normalised/fold change) available at: https://github.com/aaozmen/aaozmen

References

  1. Hu W, Nevzorova YA, Haas U et al (2014) Concurrent deletion of cyclin E1 and cyclin-dependent kinase 2 in hepatocytes inhibits DNA replication and liver regeneration in mice. Hepatology 59(2):651–660. https://doi.org/10.1002/hep.26584

    Article  CAS  Google Scholar 

  2. Taub R (2004) Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Bio 5(10):836–847. https://doi.org/10.1038/nrm1489

    Article  CAS  Google Scholar 

  3. Fausto N (2000) Liver regeneration. J Hepatol 32:19–31. https://doi.org/10.1016/S0168-8278(00)80412-2

    Article  CAS  Google Scholar 

  4. Michalopoulos GK (2010) Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. Am J Pathol 176(1):2–13. https://doi.org/10.2353/ajpath.2010.090675

    Article  CAS  Google Scholar 

  5. Abu Rmilah A, Zhou W, Nelson E et al (2019) Understanding the marvels behind liver regeneration. WIREs Dev Biol 8(e340):1–28. https://doi.org/10.1002/wdev.340

    Article  Google Scholar 

  6. Xu C, Chang C, Yuan J et al (2005) Expressed genes in regenerating rat liver after partial hepatectomy. World J Gastroenterol 11(19):2932–2940. https://doi.org/10.3748/wjg.v11.i19.2932

    Article  CAS  Google Scholar 

  7. Wang X, Herr RA, Rabelink M et al (2009) Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation substrates. J Cell Biol 187(5):655–668. https://doi.org/10.1083/jcb.200908036

    Article  CAS  Google Scholar 

  8. Kurinna S, Barton MC (2011) Cascades of transcription regulation during liver regeneration. Int J Biochem Cell B 43(2):189–197. https://doi.org/10.1016/j.biocel.2010.03.013

    Article  CAS  Google Scholar 

  9. Ciechanover A (1998) The ubiquitin—proteasome pathway: on protein death and cell life. EMBO J 17(24):7151–7160. https://doi.org/10.1093/emboj/17.24.7151

    Article  CAS  Google Scholar 

  10. Yau R, Rape M (2016) The increasing complexity of the ubiquitin code. Nat Cell Biol 18(6):579–586. https://doi.org/10.1038/ncb3358

    Article  CAS  Google Scholar 

  11. Zinngrebe J, Montinaro A, Peltzer N et al (2013) Ubiquitin in the immune system. EMBO Rep 15(1):28–45. https://doi.org/10.1002/embr.201338025

    Article  CAS  Google Scholar 

  12. Koepp DM, Harper JW, Elledge SJ (1999) How the cyclin became a cyclin: regulated proteolysis in the cell cycle. Cell 97:431–434. https://doi.org/10.1016/s0092-8674(00)80753-9

    Article  CAS  Google Scholar 

  13. Peters JM (2002) The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol Cell 9:931–943. https://doi.org/10.1016/s1097-2765(02)00540-3

    Article  CAS  Google Scholar 

  14. Wu SY, Kuan VJW, Tzeng YW et al (2016) The anaphase promoting complex works together with the SCF complex for proteolysis of the S-phase cyclin Clb6 during the transition from G1 to S phase. Fungal Genet Biol 91(2016):6–19. https://doi.org/10.1016/j.fgb.2016.03.004

    Article  CAS  Google Scholar 

  15. Garcia-Higuera I, Taniguchi T, Ganesan S et al (2001) Interaction of the Fanconi Anemia proteins and BRCA1 in a common pathway. Mol Cell 7(2):249–262. https://doi.org/10.1016/S1097-2765(01)00173-3

    Article  CAS  Google Scholar 

  16. Cheung RS, Taniguchi T (2017) Recent insights into the molecular basis of Fanconi anemia: genes, modifiers, and drivers. Int J Hematol 106(3):335–344. https://doi.org/10.1007/s12185-017-2283-4

    Article  CAS  Google Scholar 

  17. Deng CX (2002) Roles of BRCA1 in centrosome duplication. Oncogene 21:6222–6227. https://doi.org/10.1038/sj.onc.1205713

    Article  CAS  Google Scholar 

  18. Kais Z, Parvin JD (2008) Regulation of centrosomes by the BRCA1-dependent ubiquitin ligase. Cancer Biol Ther 7(10):1540–1543. https://doi.org/10.4161/cbt.7.10.7053

    Article  CAS  Google Scholar 

  19. Villa E, Marchetti S, Ricci JE (2018) No Parkin zone: mitophagy without Parkin. Trends Cell Biol 28(11):882–895. https://doi.org/10.1016/j.tcb.2018.07.004

    Article  CAS  Google Scholar 

  20. Montava-Garriga L, Ganley IG (2019) Outstanding questions in mitophagy: what we do and do not know. J Mol Biol 432(1):206–230. https://doi.org/10.1016/j.jmb.2019.06.032

    Article  CAS  Google Scholar 

  21. Youle RJ, Van Der Bliek AM (2012) Mitochondrial fission, fusion, and stress. Science 337(6098):1062–1065. https://doi.org/10.1126/science.1219855

    Article  CAS  Google Scholar 

  22. Peng J, Ren KD, Yang J et al (2016) Mitochondrial E3 ubiquitin ligase 1: a key enzyme in regulation of mitochondrial dynamics and functions. Mitochondrion 28:49–53. https://doi.org/10.1016/j.mito.2016.03.007

    Article  CAS  Google Scholar 

  23. Strand NS, Allen JM, Ghulam M, Taylor, et al (2018) Dissecting the function of Cullin-RING ubiquitin ligase complex genes in planarian regeneration. Dev Biol 433(2):210–217. https://doi.org/10.1016/j.ydbio.2017.10.011

    Article  CAS  Google Scholar 

  24. Higgins GM, Anderson RM (1931) Experimental pathology of the liver –restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–202

    Google Scholar 

  25. Tang TX, Hashimoto T, Chao LY et al (1997) Effects of partial pancreatectomy on liver regeneration in rats. J Surg Res 72(1):8–14. https://doi.org/10.1006/jsre.1997.5165

    Article  CAS  Google Scholar 

  26. Uyanoglu M, Canbek M, Aral E et al (2008) Effects of carvacrol upon the liver of rats undergoing partial hepatectomy. Phytomedicine 15(3):226–229. https://doi.org/10.1016/j.phymed.2007.06.010

    Article  CAS  Google Scholar 

  27. Gerlach C, Sakkab DY, Scholzen T et al (1997) Ki-67 expression during rat liver regeneration after partial hepatectomy. Hepatology 26(3):573–578. https://doi.org/10.1053/jhep.1997.v26.pm0009303485

    Article  CAS  Google Scholar 

  28. Vandesompele J, De Preter K, Pattyn F et al (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3(7):1–12. https://doi.org/10.1186/gb-2002-3-7-research0034

    Article  Google Scholar 

  29. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta ∆C(T)) method. Methods 408:402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  Google Scholar 

  30. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3(6):1101–1108. https://doi.org/10.1038/nprot.2008.73

    Article  CAS  Google Scholar 

  31. Tanaka T, Arai M, Minemura S et al (2014) Expression level of sonic hedgehog correlated with the speed of gastric mucosa regeneration in artificial gastric ulcers. J Gastroenterol Hepatol 29(4):736–741. https://doi.org/10.1111/jgh.12445

    Article  CAS  Google Scholar 

  32. Yu J, Gu X, Yi S (2016) Ingenuity pathway analysis of gene expression profiles in distal nerve stump following nerve injury: insights into Wallerian degeneration. Front Cell Neurosci 10(274):1–12. https://doi.org/10.3389/fncel.2016.00274

    Article  CAS  Google Scholar 

  33. Rychtrmoc D, Hubálková L, Víšková A et al (2012) Transcriptome temporal and functional analysis of liver regeneration termination. Physiol Res 61(2):77–92. https://doi.org/10.33549/physiolres.932393

    Article  Google Scholar 

  34. Fujimoto A, Totoki Y, Abe T et al (2012) Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. Nat Genet 44(7):760–764. https://doi.org/10.1038/ng.2291

    Article  CAS  Google Scholar 

  35. Motomura M, Kwon KM, Suh SJ et al (2008) Propolis induces cell cycle arrest and apoptosis in human leukemic U937 cells through Bcl-2/Bax regulation. Environ Toxicol Pharmacol 26:61–67. https://doi.org/10.1016/j.etap.2008.01.008

    Article  CAS  Google Scholar 

  36. Bruno S, Darzynkiewicz Z (1992) Cell cycle dependent expression and stability of the nuclear protein detected by Ki-67 antibody in HL-60 cells. Cell Proliferat 25(1):31–40. https://doi.org/10.1111/j.1365-2184.1992.tb01435.x

    Article  CAS  Google Scholar 

  37. Zhang J, Wan L, Dai X et al (1845) (2014) Functional characterization of anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis. BBA-Rev Cancer 2:277–293. https://doi.org/10.1016/j.bbcan.2014.02.001

    Article  CAS  Google Scholar 

  38. Caestecker KW, Van de Walle GR (2013) The role of BRCA1 in DNA double-strand repair: past and present. Exp Cell Res 319(5):575–587. https://doi.org/10.1016/j.yexcr.2012.11.013

    Article  CAS  Google Scholar 

  39. Sivakumar S, Gorbsky GJ (2015) Spatiotemporal regulation of the anaphase-promoting complex in mitosis. Nat Rev Mol Cell Bio 16(2):82–94. https://doi.org/10.1038/nrm3934

    Article  CAS  Google Scholar 

  40. Ceccaldi R, Sarangi P, D’Andrea AD (2016) The Fanconi anaemia pathway: new players and new functions. Nat Rev Mol Cell Bio 17(6):337–349. https://doi.org/10.1038/nrm.2016.48

    Article  CAS  Google Scholar 

  41. Macleod KF (2020) Mitophagy and mitochondrial dysfunction in cancer. Annu Rev Cancer Biol 4:41–60. https://doi.org/10.1146/annurev-cancerbio-030419-033405

    Article  Google Scholar 

  42. Di Bacco A, Gill G (2006) SUMO-specific proteases and the cell cycle: an essential role for SENP5 in cell proliferation. Cell Cycle 5(20):2310–2313. https://doi.org/10.4161/cc.5.20.3367

    Article  Google Scholar 

  43. Lee L, Oliva ABP, Churikov D et al (2019) UFMylation of MRE11 is essential for maintenance of telomere length and hematopoietic stem cell survival. Sci Adv. https://doi.org/10.1101/846477

    Article  Google Scholar 

  44. Zhi X, Chen C (2012) WWP1: A versatile ubiquitin E3 ligase in signaling and diseases. Cell Mol Life Sci 69(9):1425–1434. https://doi.org/10.1007/s00018-011-0871-7

    Article  CAS  Google Scholar 

  45. Cheung KF, Lam CNY, Wu K et al (2012) Characterization of the gene structure, functional significance, and clinical application of RNF180, a novel gene in gastric cancer. Cancer 118(4):947–959. https://doi.org/10.1002/cncr.26189

    Article  CAS  Google Scholar 

  46. Yang H, Wu L, Ke S et al (2016) Downregulation of ubiquitin-conjugating enzyme UBE2D3 promotes telomere maintenance and radioresistance of Eca-109 human esophageal carcinoma cells. J Cancer 7(9):1152–1162. https://doi.org/10.7150/jca.14745

    Article  CAS  Google Scholar 

  47. So CC, Ramachandran S, Martina A (2019) E3 Ubiquitin Ligases RNF20 and RNF40 are required for double-stranded break (DSB) repair: evidence for monoubiquitination of histone H2B lysine 120 as a novel axis of DSB signaling and repair. Mol Cell Biol 39(8):1–19. https://doi.org/10.1128/MCB.00488-18

    Article  Google Scholar 

  48. Liao Y, Shikapwashya ON, Shteyer E et al (2004) Delayed hepatocellular mitotic progression and impaired liver regeneration in early growth response-1-deficient mice. J Biol Chem 279(41):43107–43116. https://doi.org/10.1074/jbc.M407969200

    Article  CAS  Google Scholar 

  49. Yamaji S, Zhang M, Zhang J et al (2010) Hepatocyte-specific deletion of DDB1 induces liver regeneration and tumorigenesis. PNAS 107(51):22237–22242. https://doi.org/10.1073/pnas.1015793108

    Article  Google Scholar 

  50. Cheng R, Liang X, Zhao Q et al (2017) APC/Cdh1 controls cell cycle entry during liver regeneration. Exp Cell Res 354(2):78–84. https://doi.org/10.1016/j.yexcr.2017.03.038

    Article  CAS  Google Scholar 

  51. Bachofner M, Speicher T, Bogorad RL et al (2017) Large-scale quantitative proteomics identifies the ubiquitin ligase Nedd4-1 as an essential regulator of liver regeneration. Dev Cell 42:616–625. https://doi.org/10.1016/j.devcel.2017.07.025

    Article  CAS  Google Scholar 

  52. Ozeki A, Tsukamoto I (1999) Retinoic acid repressed the expression of c- fos and c-jun and induced apoptosis in regenerating rat liver after partial hepatectomy. BBA-Mol Cell Res 1450:308–319. https://doi.org/10.1016/S0167-4889(99)00063-4

    Article  CAS  Google Scholar 

  53. Starkel P, De Saeger C, Sempoux C et al (2005) Blunted DNA synthesis and delayed S-phase entry following inhibition of Cdk2 activity in the regenerating rat liver. Lab Invest 85(4):562–571. https://doi.org/10.1038/labinvest.3700245

    Article  CAS  Google Scholar 

  54. Steer CJ (1995) Liver regeneration. FASEB 9:1396–1400. https://doi.org/10.1016/B978-1-4160-3258-8.50007-3

    Article  CAS  Google Scholar 

  55. Mizutani T, Yokoyama Y, Kokuryo T et al (2013) Calcitonin gene e related peptide regulates the early phase of liver regeneration. J Surg Res 183(1):138–145. https://doi.org/10.1016/j.jss.2012.11.028

    Article  CAS  Google Scholar 

  56. Meier M, Andersen KJ, Knudsen AR et al (2016) Liver regeneration is dependent on the extent of hepatectomy. J Surg Res 6:5–7. https://doi.org/10.1016/j.jss.2016.06.020

    Article  Google Scholar 

  57. Matot I, Nachmansson N, Duev O et al (2018) Impaired liver regeneration after hepatectomy and bleeding is associated with a shift from hepatocyte proliferation to hypertrophy. FASEB J 31(12):5283–5295. https://doi.org/10.1096/fj.201700153R

    Article  Google Scholar 

  58. Zou Y, Bao Q, Kumar S et al (2012) Four waves of hepatocyte proliferation linked with three waves of hepatic fat accumulation during partial hepatectomy-induced liver regeneration. PLoS ONE 7(2):e30675. https://doi.org/10.1371/journal.pone.0030675

    Article  CAS  Google Scholar 

  59. Lehmann K, Tschuor C, Rickenbacher A et al (2012) Liver failure after extended hepatectomy in mice is mediated by a p21-dependent barrier to liver regeneration. Gastroenterology 143(6):1609-1619.e4. https://doi.org/10.1053/j.gastro.2012.08.043

    Article  CAS  Google Scholar 

  60. Pines J (2011) Cubism and the cell cycle: The many faces of the APC/C. Nat Rev Mol Cell Bio 12(7):427–438. https://doi.org/10.1038/nrm3132

    Article  CAS  Google Scholar 

  61. de Boer HR, Guerrero Llobet S, van Vugt MA (2016) Controlling the response to DNA damage by the APC/C-Cdh1. Cell Mol Life Sci 73(5):949–960. https://doi.org/10.1007/s00018-015-2096-7

    Article  CAS  Google Scholar 

  62. Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9(3):153–166. https://doi.org/10.1038/nrc2602

    Article  CAS  Google Scholar 

  63. Musacchio A (2015) The molecular biology of spindle assembly checkpoint signaling dynamics. Curr Biol 25(20):R1002–R1018. https://doi.org/10.1016/j.cub.2015.08.051

    Article  CAS  Google Scholar 

  64. Gmachl M, Gieffers C, Podtelejnikov AV et al (2000) The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex. PNAS 97(16):8973–8978. https://doi.org/10.1073/pnas.97.16.8973

    Article  CAS  Google Scholar 

  65. Tang Z, Li B, Bharadwaj R et al (2001) APC2 cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Mol Biol Cell 12(12):3839–3851. https://doi.org/10.1091/mbc.12.12.3839

    Article  CAS  Google Scholar 

  66. Xie C, Powell C, Yao M et al (2014) Ubiquitin-conjugating enzyme E2C: a potential cancer biomarker. Int J Biochem Cell B 47:113–117. https://doi.org/10.1016/j.biocel.2013.11.023

    Article  CAS  Google Scholar 

  67. Okamoto Y, Ozaki T, Miyazaki K et al (2003) UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme. Cancer Res 63(14):4167–4173

    CAS  Google Scholar 

  68. Ma R, Kang X, Zhang G et al (2016) High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma. Oncol Lett 11(3):2300–2304. https://doi.org/10.3892/ol.2016.4171

    Article  CAS  Google Scholar 

  69. Walker A, Acquaviva C, Matsusaka T et al (2008) UbcH10 has a rate-limiting role in G1 phase but might not act in the spindle checkpoint or as part of an autonomous oscillator. J Cell Sci 121(14):2319–2326. https://doi.org/10.1242/jcs.031591

    Article  CAS  Google Scholar 

  70. Van Ree JH, Jeganathan KB, Malureanu L et al (2010) Overexpression of the E2 ubiquitin-conjugating enzyme Ubch10 causes chromosome missegregation and tumor formation. J Cell Biol 188(1):83–100. https://doi.org/10.1083/jcb.200906147

    Article  CAS  Google Scholar 

  71. Arvand A, Bastians H, Welford SM et al (1998) EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction. Oncogene 17(16):2039–2045. https://doi.org/10.1038/sj.onc.1202129

    Article  CAS  Google Scholar 

  72. Moldovan GL, D’Andrea AD (2009) How the fanconi anemia pathway guards the genome. Annu Rev Genet 43:223–249. https://doi.org/10.1146/annurev-genet-102108-134222

    Article  CAS  Google Scholar 

  73. Jones MJK, Huang TT (2012) The Fanconi anemia pathway in replication stress and DNA crosslink repair. Cell Mol Life Sci 69(23):3963–3974. https://doi.org/10.1007/s00018-012-1051-0

    Article  CAS  Google Scholar 

  74. Fang S, Lorick KL, Jensen JP et al (2003) RING finger ubiquitin protein ligases: implications for tumorigenesis, metastasis and for molecular targets in cancer. Semin Cancer Biol 13(1):5–14. https://doi.org/10.1016/S1044-579X(02)00095-0

    Article  CAS  Google Scholar 

  75. Zeman MK, Cimprich KA (2014) Causes and consequences of replication stress. Nat Cell Biol 16(1):2–9. https://doi.org/10.1038/ncb2897

    Article  CAS  Google Scholar 

  76. Wang GP, Xu CS (2011) Alterations in DNA repair gene expression and their possible regulation in rat-liver regeneration. Genet Mol Biol 34(2):304–309. https://doi.org/10.1590/S1415-47572011005000013

    Article  Google Scholar 

  77. He W, Xiao L, Cao C et al (2016) UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSKβ/β-catenin pathway. Oncotarget 7(12):15161–15172. https://doi.org/10.18632/oncotarget.7805

    Article  Google Scholar 

  78. Vaughn JP, Davis PL, Jarboe MD et al (1996) BRCA1 expression is induced before DNA synthesis in both normal and tumor-derived breast cells. Cell Growth Differ 7(6):711–715

    CAS  Google Scholar 

  79. Lemasters JJ (2005) Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuv Res 8(1):3–5. https://doi.org/10.1089/rej.2005.8.3

    Article  CAS  Google Scholar 

  80. Ferri D, Moro L, Mastrodonato M et al (2005) Ultrastructural zonal heterogeneity of hepatocytes and mitochondria within the hepatic acinus during liver regeneration after partial hepatectomy. Biol Cell 97(4):277–288. https://doi.org/10.1042/bc20040154

    Article  CAS  Google Scholar 

  81. Guerrieri F, Vendemiale G, Grattagliano I et al (1999) Mitochondrial oxidative alterations following partial hepatectomy. Free Radic Bio Med 26(1–2):34–41. https://doi.org/10.1016/S0891-5849(98)00145-2

    Article  CAS  Google Scholar 

  82. Guerrieri F, Muolo L, Cocco T et al (1995) Correlation between rat liver regeneration and mitochondrial energy metabolism. Biochim Biophys Acta 1268:209–213. https://doi.org/10.1016/0925-4439(95)00072-c

    Article  Google Scholar 

  83. Lin CW, Chen YS, Lin CC et al (2015) Amiodarone as an autophagy promoter reduces liver injury and enhances liver regeneration and survival in mice after partial hepatectomy. Sci Rep-UK 5:15807. https://doi.org/10.1038/srep15807

    Article  CAS  Google Scholar 

  84. Palikaras K, Lionaki E, Tavernarakis N (2018) Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat Cell Biol 20(9):1013–1022. https://doi.org/10.1038/s41556-018-0176-2

    Article  CAS  Google Scholar 

  85. Fabbro M, Savage K, Hobson K et al (2004) BRCA1-BARD1 complexes are required for P53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage. J Biol Chem 279(30):31251–31258. https://doi.org/10.1074/jbc.M405372200

    Article  CAS  Google Scholar 

  86. Eifler K, Vertegaal ACO (2015) SUMOylation-mediated regulation of cell cycle progression and cancer. Trends Biochem Sci 40(12):779–793. https://doi.org/10.1016/j.tibs.2015.09.006

    Article  CAS  Google Scholar 

  87. Sarangi P, Zhao X (2015) SUMO-mediated regulation of DNA damage repair and responses. Trends Biochem Sci 40(4):233–242. https://doi.org/10.1016/j.tibs.2015.02.006

    Article  CAS  Google Scholar 

  88. Qin B, Yu J, Nowsheen S et al (2019) UFL1 promotes histone H4 ufmylation and ATM activation. Nat Commun 10:1242. https://doi.org/10.1038/s41467-019-09175-0

    Article  CAS  Google Scholar 

  89. Lam SY, Murphy C, Foley LA et al (2014) The human ubiquitin conjugating enzyme UBE2J2 (Ubc6) is a substrate for proteasomal degradation. Biochem Bioph Res Co 451(3):361–366. https://doi.org/10.1016/j.bbrc.2014.07.099

    Article  CAS  Google Scholar 

  90. Oh E, Akopian D, Rape M (2018) Principles of ubiquitin- dependent signaling. Annu Rev Cell Dev Bi 34:137–162. https://doi.org/10.1146/annurev-cellbio-100617-062802

    Article  CAS  Google Scholar 

  91. Li Y, Zhou Z, Chen C (2008) WW domain-containing E3 ubiquitin protein ligase 1 targets p63 transcription factor for ubiquitin-mediated proteasomal degradation and regulates apoptosis. Cell Death Differ 15(12):1941–1951. https://doi.org/10.1038/cdd.2008.134

    Article  CAS  Google Scholar 

  92. Hu J, Cui F, Xv Z et al (2020) PNO1 promotes cell proliferation in prostate cancer. https://doi.org/10.21203/rs.2.17848/v3

  93. Watson ER, Brown NG, Peters JM et al (2019) Posing the APC/C E3 ubiquitin ligase to orchestrate cell division. Trends Cell Biol 29(2):117–134. https://doi.org/10.1016/j.tcb.2018.09.007

    Article  CAS  Google Scholar 

  94. Zhang Y, Zhou H (2020) LncRNA BCAR4 promotes liver cancer progression by upregulating ANAPC11 expression through sponging miR-1261. Int J Mol Med 46(1):159–166. https://doi.org/10.3892/ijmm.2020.4586

    Article  CAS  Google Scholar 

  95. Yi Q, Liu Z, Zhang K et al (2021) The role of long non-coding RNA BCAR4 in human cancers. Hum Cell 34:1301–1309. https://doi.org/10.1007/s13577-021-00556-6

    Article  CAS  Google Scholar 

  96. Lee YR, Chen M, Lee JD et al (2019) Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway. Science 364:6441-eaau0159. https://doi.org/10.1126/science.aau0159

    Article  CAS  Google Scholar 

  97. Komuro A, Imamura T, Saitoh M et al (2004) Negative regulation of transforming growth factor-ß (TGF-ß) signaling by WW domain-containing protein 1 (WWP1). Oncogene 23:6914–6923. https://doi.org/10.1038/sj.onc.1207885

    Article  CAS  Google Scholar 

  98. Udali S, Guarini P, Ruzzenente A et al (2015) DNA metylation and gene expression profiles show novel regulatory pathways in hepatocellular carcinoma. Clin Epigenetics 7(43):1–13. https://doi.org/10.1186/s13148-015-0077-1

    Article  CAS  Google Scholar 

  99. Zheng X, Chen K, Liu X et al (2018) High RNF40 expression indicates poor prognosis of hepatocellular carcinoma. Int J Clin Exp Pathol 11(5):2901–2906

    Google Scholar 

  100. Guan GG, Wang WB, Lei BX et al (2015) UBE2D3 is a positive prognostic factor and is negatively correlated with hTERT expression in esophageal cancer. Oncol Lett 9(4):1567–1574. https://doi.org/10.3892/ol.2015.2926

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Thanks to Prof. Dr. Didem TURGUT COŞAN for her valuable contributions

Funding

This study is funded by Eskisehir Osmangazi University Project Office, Project number 201719040.

Author information

Authors and Affiliations

Authors

Contributions

AOY Writing the article, Gene expression analysing, experimental design, Western blotting, rats surgery. MC Funding acquisition, project administration, Supervision, doing histological section and participated in discussion.

Corresponding author

Correspondence to Ayse Ozmen Yaylaci.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ozmen Yaylaci, A., Canbek, M. The role of ubiquitin signaling pathway on liver regeneration in rats. Mol Cell Biochem 478, 131–147 (2023). https://doi.org/10.1007/s11010-022-04482-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-022-04482-5

Keywords

Navigation