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Oncogene. 2003 Oct 30;22(49):7762-73.

p53-independent induction of Gadd45 by histone deacetylase inhibitor: coordinate regulation by transcription factors Oct-1 and NF-Y.

Author information

1
Department of Preventive Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.

Abstract

Histone deacetylase (HDAC) inhibitors cause growth arrest at the G1 and/or G2/M phases, and induce differentiation and/or apoptosis in a wide variety of tumour cells. The growth arrest at G1 phase by HDAC inhibitors is thought to be highly dependent on the upregulation of p21/WAF1, but the precise mechanism by which HDAC inhibitors cause G2/M arrest or apoptosis in tumour cells is unknown. Gadd45 causes cell cycle arrest at the G2/M phase transition and participates in genotoxic stress-induced apoptosis. We show here that it is also induced by a typical HDAC inhibitor, trichostatin A (TSA), through its promoter, in a p53-independent manner. To identify the mechanism of activation of the gadd45 promoter, we performed luciferase reporter analyses and electrophoretic mobility shift assays. These revealed that both the Oct-1 and CCAAT sites are needed for the full activation by TSA. We also found that the transcription factors Oct-1 and NF-Y specifically bind to each site. Thus, HDAC inhibitors can induce Gadd45 through its promoter without the need for functional p53, and both the Oct-1 and NF-Y concertedly participate in TSA-induced activation of the gadd45 promoter.

PMID:
14586402
DOI:
10.1038/sj.onc.1207091
[Indexed for MEDLINE]

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