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Oncogene. 2010 May 6;29(18):2659-71. doi: 10.1038/onc.2010.19. Epub 2010 Feb 15.

An HDAC1-binding domain within FATS bridges p21 turnover to radiation-induced tumorigenesis.

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  • 1Department of Biochemistry and Molecular Biology, Key Laboratory of Ministry of Education for Breast Cancer Prevention and Treatment, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. zhengli@tijmu.edu.cn

Abstract

There is a gap between the initial formation of cells carrying radiation-induced genetic damage and their contribution to cancer development. Herein, we reveal a previously uncharacterized gene FATS through a genome-wide approach and demonstrate its essential role in regulating the abundance of p21 in surveillance of genome integrity. A large exon coding the NH2-terminal domain of FATS, deleted in spontaneous mouse lymphomas, is much more frequently deleted in radiation-induced mouse lymphomas. Its human counterpart is a fragile site gene at a previously identified loss of heterozygosity site. FATS is essential for maintaining steady-state level of p21 protein and sustaining DNA damage checkpoint. Furthermore, the NH2-terminal FATS physically interacts with histone deacetylase 1 (HDAC1) to enhance the acetylation of endogenous p21, leading to the stabilization of p21. Our results reveal a molecular linkage between p21 abundance and radiation-induced carcinogenesis.

PMID:
20154723
[PubMed - indexed for MEDLINE]
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