Reference : HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-depende...
Scientific journals : Article
Human health sciences : Oncology
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/18457
HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism.
English
Mottet, Denis mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Pirotte, Sophie mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Lamour, Virginie mailto [Université de Liège - ULg > > Centre facultaire de rech. en cancérologie expérimentale >]
Hagedorn, M. [> > > >]
Javerzat, S. [> > > >]
Bikfalvi, A. [> > > >]
Bellahcene, Akeila mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire - GIGA-R : Labo de recherche sur les métastases >]
Verdin, Eric [ > > ]
2009
Oncogene
Nature Publishing Group
28
2
243-56
Yes (verified by ORBi)
International
0950-9232
1476-5594
Basingstoke
United Kingdom
[en] histone deacetylase ; p21 ; Sp1 ; siRNA ; cancer
[en] 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 p21(WAF1/Cip1)gene. The HDACs that regulate p21(WAF1/Cip1) are not fully identified. Using small interfering RNAs, we found that HDAC4 participates in the repression of p21(WAF1/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 p21(WAF1/Cip1) proximal promoter, suggesting a key role for Sp1 in HDAC4-mediated repression of p21(WAF1/Cip1). Induction of p21(WAF1/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.
Giga-Cancer
European FP6 STROMA ; European FP6 METABRE ; Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Centre Anticancéreux près l'Université de Liège ; Fonds Léon Fredericq ; Interuniveristy Attraction Pole Program - Belgian Science Policy (IAP 5/31) ; TELEVIE
http://hdl.handle.net/2268/18457
10.1038/onc.2008.371

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