Transcriptional repression of p21((Waf1/Cip1/Sdi1)) gene by c-jun through Sp1 site

Chih Hung Wang, Yeou Ping Tsao, Huei Jane Chen, Hui Ling Chen, Hsing Won Wang, Show Li Chen

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Previously, we found that c-jun represses the tumor suppressor p21((Waf1/Cip1/Sdi1)) (p21) gene expression. In this study, we further investigated the mechanism of the inhibitory effect of c-jun on p21. After analysis of a series of deletion and point mutants of p21 promoter, we found that Sp1-3 site (-77 and -83) relative to the transcription start site played an important role for c-jun-repressing-responsive element in the p21 promoter. Both Sp1 and Sp3 transcription factors were the key factors for this event. However, the data from electrophoretic mobility shift assay indicated that c-jun did not change the Sp1 DNA-binding affinity, suggesting that additional factors may be involved in the repression of p21 by c-jun. Furthermore, c-jun could inhibit butyrate-inducing p21 gene expression through Sp1, indicating at least one common pathway whereby p21 expression is affected by c-jun and butyrate in opposing actions. Moreover, the hyperphosphorylated retinoblastoma protein (Rb) increased in c-jun expressing cells, indicating that phosphorylated Rb may play a role in regulating Sp1 to repress p21 expression. This is the first demonstration of how housekeeping factors and oncogene product counteract the function of tumor suppressor genes to control cell cycle progression. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)303-310
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume270
Issue number1
DOIs
Publication statusPublished - Apr 2 2000
Externally publishedYes

Keywords

  • c-jun
  • p21
  • Sp1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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