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

• DOI: 10.1038/onc.2010.19
• Publication Date: 2010-02-15T11:19:22Z
• Authors: Z Li; Q Zhang; J-H Mao; A Weise; K Mrasek; X Fan; X Zhang; T Liehr; K H Lu; A Balmain; W-W Cai
• Keywords: HDAC1

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.