De-SUMOylation on ATF3 Enhances p53-ATF3 Binding and Trans-activation of p53 Responsive Promoter but not p53 Stability

Chiung-Min Wang, Wei-Hsiung Yang

Abstract


Cyclic AMP-dependent transcription factor-3 (ATF3), a stress sensor and mediator, plays an essential role in cells to maintain homeostatsis and has diverse functions in cellular survival and death signal pathways. Previously, we demonstrated that ATF3 can be SUMOylfig

ated in vitro and in vivo and lysine 42 is the main SUMO site. Several reports have shown that ATF3 is a novel regulator of p53 protein stability and function; however, the role of ATF3 SUMOylation on ATF3-p53 interaction and p53 stability as well as p53-dependent transcriptional activity remains unknown. Here we report that de-SUMOylation of ATF3 enhanced ATF3-p53 physical interaction. While overexpression of ATF3 stabilizes p53, SUMOylation status of ATF3 does not alter ATF3-mediated p53 stability. Interestingly, de-SUMOylation of ATF3 augmented trans-activation of p53 responsive promoters, including natural p53-dependent promoters. Taken together, we provide the evidence that SUMOylation of ATF3 regulates ATF3-p53 interaction and transactivation of p53 responsive promoter.


Keywords


ATF3, p53, SUMO

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References


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