TAp73 is a downstream target of p53 in controlling the cellular defense against stress.
TAp73 is a p53 tumor suppressor gene homologue that is known to be mainly involved in apoptosis. We report here that TAp73 is necessary for the cellular response to oxidative stress and that TAp73 functions as a downstream target of p53 in this process. We show that p53 physically interacts with the TAp73 promoter under stress conditions that lead to cell death. Particularly, p53 binds to a palindromic site in the TAp73 promoter, activates the promoter of TAp73, and selectively induces TAp73 transcription. TAp73 expression is highly increased under oxidative stress in a p53-dependent manner. Furthermore, knock-down of TAp73 expression inhibits the cellular apoptotic response to oxidative damage. In contrast, the ectopic expression of TAp73 in p53(-/-) mouse embryonic fibroblasts induces oxidative cell death. Our findings demonstrate that p53 is a direct transcriptional regulator of TAp73. Our data reveal a new pathway for cellular protection against oxidative damage and provide evidence that TAp73 is a stress-response gene and a downstream effector in the p53 pathway.
Wang
Jianli
J
Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Liu
Yu-Xin
YX
Hande
M Prakash
MP
Wong
Alan C
AC
Jin
Y Jenny
YJ
Yin
Yuxin
Y
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C495901:TP53 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C454920:delta Np73, mouse