DNA damage induces expression of WWP1 to target ΔNp63α to degradation.

Autor: Chen, Ji, Shi, Hua, Chen, Yonglong, Fan, Shijie, Liu, Dingyi, Li, Chenghua
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Zdroj: PLoS ONE; 4/20/2017, Vol. 12 Issue 4, p1-9, 9p
Abstrakt: ΔNp63αplays key roles in cell survival and proliferation. So its expression is always tightly controlled in cells. We previously reported that DNA damage down-regulates transcription of ΔNp63αin FaDu and HaCat cells, which contributes to cell apoptosis. In the present study, we found that DNA damage induces down-regulation of ΔNp63αvia facilitating its proteasomal degradation in cell lines such as MDA-MB-231 and MCF10A. Further investigation revealed that transcription of WWP1 is stimulated by DNA damage in these cells. Knock-down of WWP1 abrogates DNA damage-induced down-regulation of ΔNp63αand partially rescues cell apoptosis. Interestingly, DNA damage may stimulate WWP1 through different mechanisms in different cell types: it up-regulates transcription of WWP1 in a p53-dependent manner in MCF10A and HEK293 cells, while miR-452 may be involved in DNA damage-induced up-regulation of WWP1 in MDA-MB-231 cells. Our study demonstrates a novel pathway which regulates ΔNp63αupon cellular response to chemotherapeutic agents. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index