FATS is a transcriptional target of p53 and associated with antitumor activity.
Frequent mutations of p53 in human cancers exemplify its crucial role as a tumor suppressor transcription factor, and p21, a transcriptional target of p53, plays a central role in surveillance of cell-cycle checkpoints. Our previous study has shown that FATS stabilize p21 to preserve genome integrity. In this study we identified a novel transcript variant of FATS (GenBank: GQ499374) through screening a cDNA library from mouse testis, which uncovered the promoter region of mouse FATS. Mouse FATS was highly expressed in testis. The p53-responsive elements existed in proximal region of both mouse and human FATS promoters. Functional study indicated that the transcription of FATS gene was activated by p53, whereas such effect was abolished by site-directed mutagenesis in the p53-RE of FATS promoter. Furthermore, the expression of FATS increased upon DNA damage in a p53-dependent manner. FATS expression was silent or downregulated in human cancers, and overexpression of FATS suppressed tumorigenicity in vivo independently of p53. Our results reveal FATS as a p53-regulated gene to monitor genomic stability.
Zhang
Xifeng
X
Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Zhang
Qian
Q
Zhang
Jun
J
Qiu
Li
L
Yan
Shuang-Shuang
SS
Feng
Juling
J
Sun
Yan
Y
Huang
Xingxu
X
Lu
Karen H
KH
Li
Zheng
Z
D000818:Animals; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D016513:Mice, SCID; D016297:Mutagenesis, Site-Directed; D009369:Neoplasms; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53