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- Title
An HDAC1-binding domain within FATS bridges p21 turnover to radiation-induced tumorigenesis.
- Authors
Li, Z; Zhang, Q; Mao, J-H; Weise, A; Mrasek, K; Fan, X; Zhang, X; Liehr, T; Lu, K H; Balmain, A; Cai, W-W
- 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.
- Publication
Oncogene, 2010, Vol 29, Issue 18, p2659
- ISSN
1476-5594
- Publication type
Journal Article
- DOI
10.1038/onc.2010.19