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- Title
HDAC4 represses p21<sup>WAF1/Cip1</sup> expression in human cancer cells through a Sp1-dependent, p53-independent mechanism.
- Authors
Mottet, D; Pirotte, S; Lamour, V; Hagedorn, M; Javerzat, S; Bikfalvi, A; Bellahcène, A; Verdin, E; Castronovo, V
- Abstract
Cancer cells have complex, unique characteristics that distinguish them from normal cells, such as increased growth rates and evasion of anti-proliferative signals. Global inhibition of class I and II histone deacetylases (HDACs) stops cancer cell proliferation in vitro and has proven effective against cancer in clinical trials, at least in part, through transcriptional reactivation of the p21WAF1/Cip1gene. The HDACs that regulate p21WAF1/Cip1 are not fully identified. Using small interfering RNAs, we found that HDAC4 participates in the repression of p21WAF1/Cip1 through Sp1/Sp3-, but not p53-binding sites. HDAC4 interacts with Sp1, binds and reduces histone H3 acetylation at the Sp1/Sp3 binding site-rich p21WAF1/Cip1 proximal promoter, suggesting a key role for Sp1 in HDAC4-mediated repression of p21WAF1/Cip1. Induction of p21WAF1/Cip1 mediated by silencing of HDAC4 arrested cancer cell growth in vitro and inhibited tumor growth in an in vivo human glioblastoma model. Thus, HDAC4 could be a useful target for new anti-cancer therapies based on selective inhibition of specific HDACs.Oncogene (2009) 28, 243–256; doi:10.1038/onc.2008.371; published online 13 October 2008
- Publication
Oncogene, 2009, Vol 28, Issue 2, p243
- ISSN
0950-9232
- Publication type
Academic Journal
- DOI
10.1038/onc.2008.371