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WT1 Interacts with p53 and Inhibits p53‐induced p21 gene expression
Author(s) -
Ko Kyoung-Won,
Choe Yun-Jeong,
Lee Sun-Young,
Kim Ho-Shik
Publication year - 2012
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.26.1_supplement.734.2
Subject(s) - transactivation , mdm2 , gene knockdown , transcription factor , cancer research , tumor suppressor gene , small interfering rna , suppressor , biology , programmed cell death , transcription (linguistics) , microbiology and biotechnology , gene , carcinogenesis , apoptosis , transfection , genetics , linguistics , philosophy
Wilms’ tumor suppressor gene 1 (WT1) encodes a transcription factor important for normal cellular development and cell survival. Previous studies have reported both physical and functional interaction between the WT1 and p53 proteins. However, the relationship between WT1 and p53 has not yet been fully clarified. Here we show that WT1 retards p53‐induced transcriptional activation of p21. Using domain deletion mutant constructs of p53, we determined that C‐terminal region containing DNA‐binding domain of p53 was necessary for the interaction between WT1 and p53. In osteosarcoma U2OS cells, WT1 enhanced cell death by nutlin‐3, an antagonist of MDM2, and restrained p53‐mediated p21 expression. Consistently, p53‐induced transactivation of p21 was attenuated by WT1. Moreover, small interfering RNA‐mediated knockdown of p21 expression enhanced nutlin‐3‐induced cell death. Taken together, WT1 interacts with p53 and inhibits p53‐ induced p21, leading to potentiation of p53‐induced cell death. This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education, Science and Technology (2011‐ 0027115).