Abstract
Transforming growth factor β-stimulated clone 22 domain family, member 2 (TSC22D2), a member of the TSC22D family, has been implicated as a tumor-associated gene, but its function remains unknown. To further explore its biological role, yeast two-hybrid screening combined with multiple bioinformatics tools was used to identify 44 potential interacting partners of the TSC22D2 protein that were mainly involved in gene transcription, cellular metabolism, and cell cycle regulation. The protein WD repeat domain 77 (WDR77) was selected for further validation due to its function in the cell cycle and tumor development, as well as its high detection frequency in the yeast two-hybrid assay. Immunoprecipitation and immunofluorescence experiments confirmed an interaction between the TSC22D2 and WDR77 proteins. Our work greatly expands the putative protein interaction network of TSC22D2 and provides deeper insight into the biological functions of the TSC22D2 and WDR77 proteins.
Similar content being viewed by others
References
Liang F, Zeng Z, Li Q, Li X, Li Z, Gong Z, et al. TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer. Int J Oncol. 2016 (in press).
Shibanuma M, Kuroki T, Nose K. Isolation of a gene encoding a putative leucine zipper structure that is induced by transforming growth factor beta 1 and other growth factors. J Biol Chem. 1992;267:10219–24.
Kester HA, Blanchetot C, den Hertog J, van der Saag PT, van der Burg B. Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity. J Biol Chem. 1999;274:27439–47.
Fiol DF, Mak SK, Kultz D. Specific TSC22 domain transcripts are hypertonically induced and alternatively spliced to protect mouse kidney cells during osmotic stress. Febs J. 2007;274:109–24.
Ohta S, Yanagihara K, Nagata K. Mechanism of apoptotic cell death of human gastric carcinoma cells mediated by transforming growth factor beta. Biochem J. 1997;324(Pt 3):777–82.
D'Adamio F, Zollo O, Moraca R, Ayroldi E, Bruscoli S, Bartoli A, et al. A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR/CD3-activated cell death. Immunity. 1997;7:803–12.
Dohrmann CE, Belaoussoff M, Raftery LA. Dynamic expression of TSC-22 at sites of epithelial-mesenchymal interactions during mouse development. Mech Dev. 1999;84:147–51.
Gluderer S, Brunner E, Germann M, Jovaisaite V, Li C, Rentsch CA, et al. Madm (Mlf1 adapter molecule) cooperates with Bunched A to promote growth in Drosophila. J Biol. 2010;9:9.
Canterini S, Bosco A, Carletti V, Fuso A, Curci A, Mangia F, et al. Subcellular TSC22D4 localization in cerebellum granule neurons of the mouse depends on development and differentiation. Cerebellum. 2012;11:28–40.
Beaulieu E, Morand EF. Role of GILZ in immune regulation, glucocorticoid actions and rheumatoid arthritis. Nat Rev Rheumatol. 2011;7:340–8.
Riccardi C. GILZ (glucocorticoid-induced leucine zipper), a mediator of the anti-inflammatory and immunosuppressive activity of glucocorticoids. Ann Ig. 2010;22:53–9.
Riccardi C, Zollo O, Nocentini G, Bruscoli S, Bartoli A, D'Adamio F, et al. Glucocorticoid hormones in the regulation of cell death. Therapie. 2000;55:165–9.
Kawamata H, Nakashiro K, Uchida D, Hino S, Omotehara F, Yoshida H, et al. Induction of TSC-22 by treatment with a new anti-cancer drug, vesnarinone, in a human salivary gland cancer cell. Br J Cancer. 1998;77:71–8.
Shostak KO, Dmitrenko VV, Vudmaska MI, Naidenov VG, Beletskii AV, Malisheva TA, et al. Patterns of expression of TSC-22 protein in astrocytic gliomas. Exp Oncol. 2005;27:314–8.
Iida M, Anna CH, Gaskin ND, Walker NJ, Devereux TR. The putative tumor suppressor Tsc-22 is downregulated early in chemically induced hepatocarcinogenesis and may be a suppressor of Gadd45b. Toxicol Sci. 2007;99:43–50.
Yu J, Ershler M, Yu L, Wei M, Hackanson B, Yokohama A, et al. TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia. Blood. 2009;113:5558–67.
Yoon CH, Rho SB, Kim ST, Kho S, Park J, Jang IS, et al. Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer. Plos One. 2012;7:e42006.
Nakamura M, Kitaura J, Enomoto Y, Lu Y, Nishimura K, Isobe M, et al. Transforming growth factor-beta-stimulated clone-22 is a negative-feedback regulator of Ras/Raf signaling: implications for tumorigenesis. Cancer Sci. 2012;103:26–33.
Ayroldi E, Zollo O, Bastianelli A, Marchetti C, Agostini M, Di Virgilio R, et al. GILZ mediates the antiproliferative activity of glucocorticoids by negative regulation of Ras signaling. J Clin Invest. 2007;117:1605–15.
Ayroldi E, Petrillo MG, Bastianelli A, Marchetti MC, Ronchetti S, Nocentini G, et al. L-GILZ binds p53 and MDM2 and suppresses tumor growth through p53 activation in human cancer cells. Cell Death Differ. 2015;22:118–30.
Zhou L, Wu H, Lee P, Wang Z. Roles of the androgen receptor cofactor p44 in the growth of prostate epithelial cells. J Mol Endocrinol. 2006;37:283–300.
Gao S, Wang Z. Subcellular localization of p44/WDR77 determines proliferation and differentiation of prostate epithelial cells. Plos One. 2012;7:e49173.
Peng Y, Chen F, Melamed J, Chiriboga L, Wei J, Kong X, et al. Distinct nuclear and cytoplasmic functions of androgen receptor cofactor p44 and association with androgen-independent prostate cancer. Proc Natl Acad Sci U S A. 2008;105:5236–41.
Liang JJ, Wang Z, Chiriboga L, Greco MA, Shapiro E, Huang H, et al. The expression and function of androgen receptor coactivator p44 and protein arginine methyltransferase 5 in the developing testis and testicular tumors. J Urol. 2007;177:1918–22.
Ligr M, Patwa RR, Daniels G, Pan L, Wu X, Li Y, et al. Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer. Plos One. 2011;6:e26250.
Peng Y, Li Y, Gellert LL, Zou X, Wang J, Singh B, et al. Androgen receptor coactivator p44/Mep50 in breast cancer growth and invasion. J Cell Mol Med. 2010;14:2780–9.
Gu Z, Zhang F, Wang ZQ, Ma W, Davis RE, Wang Z. The p44/wdr77-dependent cellular proliferation process during lung development is re-activated in lung cancer. Oncogene. 2013;32:1888–900.
Spyrou I, Sifakis S, Ploumidis A, Papalampros AE, Felekouras E, Tsatsakis AM, et al. Expression profile of CYP1A1 and CYP1B1 enzymes in endometrial tumors. Tumor Biol. 2014;35:9549–56.
Zeng Z, Bo H, Gong Z, Lian Y, Li X, Li X, et al. AFAP1-AS1, a long noncoding RNA upregulated in lung cancer and promotes invasion and metastasis. Tumor Biol. 2015.
Liu XF, Bera TK, Kahue C, Escobar T, Fei Z, Raciti GA, et al. ANKRD26 and its interacting partners TRIO, GPS2, HMMR and DIPA regulate adipogenesis in 3T3-L1 cells. Plos One. 2012;7:e38130.
Chai Y, Liu X, Dai L, Li Y, Liu M, Zhang JY. Overexpression of HCC1/CAPERalpha may play a role in lung cancer carcinogenesis. Tumor Biol. 2014;35:6311–7.
Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S, Madden TL. NCBI BLAST: a better web interface. Nucleic Acids Res. 2008;36:W5–9.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13:2498–504.
Chatr-Aryamontri A, Breitkreutz BJ, Oughtred R, Boucher L, Heinicke S, Chen D, et al. The BioGRID interaction database: 2015 update. Nucleic Acids Res. 2015;43:D470–8.
Licata L, Briganti L, Peluso D, Perfetto L, Iannuccelli M, Galeota E, et al. MINT, the molecular interaction database: 2012 update. Nucleic Acids Res. 2012;40:D857–61.
Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43:D447–52.
Mitchell A, Chang HY, Daugherty L, Fraser M, Hunter S, Lopez R, et al. The InterPro protein families database: the classification resource after 15 years. Nucleic Acids Res. 2015;43:D213–21.
Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.
Safran M, Dalah I, Alexander J, Rosen N, Iny ST, Shmoish M, et al. GeneCards Version 3: the human gene integrator. Database (Oxford). 2010;2010:q20.
Ito T, Chiba T, Ozawa R, Yoshida M, Hattori M, Sakaki Y. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci U S A. 2001;98:4569–74.
Formstecher E, Aresta S, Collura V, Hamburger A, Meil A, Trehin A, et al. Protein interaction mapping: a Drosophila case study. Genome Res. 2005;15:376–84.
Riccardi C, Bruscoli S, Ayroldi E, Agostini M, Migliorati G. GILZ, a glucocorticoid hormone induced gene, modulates T lymphocytes activation and death through interaction with NF-kB. Adv Exp Med Biol. 2001;495:31–9.
Ayroldi E, Zollo O, Macchiarulo A, Di Marco B, Marchetti C, Riccardi C. Glucocorticoid-induced leucine zipper inhibits the Raf-extracellular signal-regulated kinase pathway by binding to Raf-1. Mol Cell Biol. 2002;22:7929–41.
Vago JP, Tavares LP, Garcia CC, Lima KM, Perucci LO, Vieira EL, et al. The role and effects of glucocorticoid-induced leucine zipper in the context of inflammation resolution. J Immunol. 2015;194:4940–50.
Wilson CH, Crombie C, van der Weyden L, Poulogiannis G, Rust AG, Pardo M, et al. Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation. Embo J. 2012;31:2486–97.
Ruiz C, Oeggerli M, Germann M, Gluderer S, Stocker H, Andreozzi M, et al. High NRBP1 expression in prostate cancer is linked with poor clinical outcomes and increased cancer cell growth. Prostate. 2012;72:1678–87.
Kerr JS, Wilson CH. Nuclear receptor-binding protein 1: a novel tumour suppressor and pseudokinase. Biochem Soc Trans. 2013;41:1055–60.
Hilt W, Wolf DH. Proteasomes: destruction as a programme. Trends Biochem Sci. 1996;21:96–102.
Smith DK, Xue H. Sequence profiles of immunoglobulin and immunoglobulin-like domains. J Mol Biol. 1997;274:530–45.
Bateman A, Sandford R. The PLAT domain: a new piece in the PKD1 puzzle. Curr Biol. 1999;9:R588–90.
Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP. Sticky fingers: zinc-fingers as protein-recognition motifs. Trends Biochem Sci. 2007;32:63–70.
Hino S, Kawamata H, Uchida D, Omotehara F, Miwa Y, Begum NM, et al. Nuclear translocation of TSC-22 (TGF-beta-stimulated clone-22) concomitant with apoptosis: TSC-22 as a putative transcriptional regulator. Biochem Biophys Res Commun. 2000;278:659–64.
Friesen WJ, Wyce A, Paushkin S, Abel L, Rappsilber J, Mann M, et al. A novel WD repeat protein component of the methylosome binds Sm proteins. J Biol Chem. 2002;277:8243–7.
Antonysamy S, Bonday Z, Campbell RM, Doyle B, Druzina Z, Gheyi T, et al. Crystal structure of the human PRMT5:MEP50 complex. Proc Natl Acad Sci U S A. 2012;109:17960–5.
Ho MC, Wilczek C, Bonanno JB, Xing L, Seznec J, Matsui T, et al. Structure of the arginine methyltransferase PRMT5-MEP50 reveals a mechanism for substrate specificity. Plos One. 2013;8:e57008.
Yi P, Gao S, Gu Z, Huang T, Wang Z. P44/WDR77 restricts the sensitivity of proliferating cells to TGFbeta signaling. Biochem Biophys Res Commun. 2014;450:409–15.
Choi SJ, Moon JH, Ahn YW, Ahn JH, Kim DU, Han TH. Tsc-22 enhances TGF-beta signaling by associating with Smad4 and induces erythroid cell differentiation. Mol Cell Biochem. 2005;271:23–8.
Uchida D, Omotehara F, Nakashiro K, Tateishi Y, Hino S, Begum NM, et al. Posttranscriptional regulation of TSC-22 (TGF-beta-stimulated clone-22) gene by TGF-beta 1. Biochem Biophys Res Commun. 2003;305:846–54.
Gupta RA, Sarraf P, Brockman JA, Shappell SB, Raftery LA, Willson TM, et al. Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22. J Biol Chem. 2003;278:7431–8.
Acknowledgments
This study was supported in part by grants from The National Natural Science Foundation of China (81272298, 81372907, 81472531, and 81572787) and the Natural Science Foundation of Hunan Province (14JJ1010 and 2015JJ1022).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflicts of interest
None
Rights and permissions
About this article
Cite this article
Li, Q., Chen, P., Zeng, Z. et al. Yeast two-hybrid screening identified WDR77 as a novel interacting partner of TSC22D2. Tumor Biol. 37, 12503–12512 (2016). https://doi.org/10.1007/s13277-016-5113-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-016-5113-z