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Selenoprotein W regulates tumor suppressor p53 in prostate epithelial cells
Author(s) -
Hawkes Wayne Chris,
Printsev Ignat,
Alkan Zeynep
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.218.6
Subject(s) - gene silencing , cell cycle checkpoint , cell cycle , microbiology and biotechnology , biology , e2f , kinase , transcription factor , cyclin dependent kinase , cell growth , dna damage , cancer research , dna repair , apoptosis , gene , dna , genetics
The anticancer activity of selenium has been demonstrated in myriad animal and in vitro studies, but the mechanisms remain obscure. Selenoprotein W (SEPW1) is a highly conserved protein of unknown function ubiquitously expressed in animals, bacteria and archea that modulates control of cell cycle entry. The tumor suppressor protein p53 is a redox‐active transcription factor that is activated by and responds to various types of stresses with apoptosis, cell cycle arrest, senescence, DNA repair, cell metabolism changes, or autophagy. TP53 is the most frequently mutated gene in human cancers. We set out to examine the functional and biochemical interactions between SEPW1 and p53. SEPW1 silencing increased p53 protein levels by decreasing p53 turnover, suggesting SEPW1 promotes cell cycle progression by destabilizing p53. Silencing SEPW1 greatly increased expression of p21(Cip1/WAF1), the cyclin‐dependent kinase inhibitor responsible for p53‐mediated cell cycle arrest. Western blots did not show any difference in phosphorylation of p53 on Ser15, suggesting a non‐canonical mechanism of p53 regulation. SEPW1 silencing increased mRNAs of stabilizers of p53 (LATS2, GMCL1, TGFB1, ZNF148, YWHAE) and decreased mRNAs of destabilizers of p53 (PIM3, RCHY1, HSPB1), suggesting several possible mechanisms for regulation of p53 by SEPW1. Supported by USDA CRIS Projects 5306‐51530‐014‐00D and 5306‐51530‐018‐00D.