TY - JOUR T1 - An HDAC1-binding domain within FATS bridges p21 turnover to radiation-induced tumorigenesis. JF - Oncogene Y1 - 2010 A1 - Li, Z A1 - Zhang, Q A1 - Jiang-Hua Mao A1 - Weise, A A1 - Mrasek, K A1 - Fan, X A1 - Zhang, X A1 - Liehr, T A1 - Lu, K H A1 - Balmain, A A1 - Cai, W-W KW - Acetylation KW - Animals KW - Binding Sites KW - Cell Division KW - Chromosome Fragile Sites KW - Cyclin-Dependent Kinase Inhibitor p21 KW - DNA Damage KW - G2 Phase KW - Histone Deacetylase 1 KW - Humans KW - Mice KW - Neoplasms, Radiation-Induced KW - NIH 3T3 Cells KW - Tumor Suppressor Proteins KW - Ubiquitination AB -

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.

VL - 29 IS - 18 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20154723?dopt=Abstract ER -