%0 Journal Article %J Oncogene %D 2010 %T An HDAC1-binding domain within FATS bridges p21 turnover to radiation-induced tumorigenesis. %A Li, Z %A Zhang, Q %A Jiang-Hua Mao %A Weise, A %A Mrasek, K %A Fan, X %A Zhang, X %A Liehr, T %A Lu, K H %A Balmain, A %A Cai, W-W %K Acetylation %K Animals %K Binding Sites %K Cell Division %K Chromosome Fragile Sites %K Cyclin-Dependent Kinase Inhibitor p21 %K DNA Damage %K G2 Phase %K Histone Deacetylase 1 %K Humans %K Mice %K Neoplasms, Radiation-Induced %K NIH 3T3 Cells %K Tumor Suppressor Proteins %K Ubiquitination %X

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.

%B Oncogene %V 29 %P 2659-71 %8 2010 May 6 %G eng %N 18 %1 http://www.ncbi.nlm.nih.gov/pubmed/20154723?dopt=Abstract %R 10.1038/onc.2010.19