Piwil2 inhibits keratin 8 degradation through promoting p38-induced phosphorylation to resist Fas-mediated apoptosis.

Siyuan Jiang, Lianfang Zhao, Yilu Lu, Meiling Wang, Yuan Chen, Dachang Tao, Yunqiang Liu, Huaqin Sun, Sizhong Zhang, Yongxin Ma

Molecular and cellular biology 2014 Nov

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The piwi-like 2 (piwil2) gene is widely expressed in tumors and protects cells from apoptosis induced by a variety of stress stimuli. However, the role of Piwil2 in Fas-mediated apoptosis remains unknown. Here, we present evidence that Piwil2 inhibits Fas-mediated apoptosis. By a bacterial two-hybrid screening, we identify a new Piwil2-interacting partner, keratin 8 (K8), a major intermediate filament protein protecting the cell from Fas-mediated apoptosis. Our results show that Piwil2 binds to K8 and p38 through its PIWI domain and forms a Piwil2/K8/P38 triple protein-protein complex. Thus, Piwil2 increases the phosphorylation level of K8 Ser-73 and then inhibits ubiquitin-mediated degradation of K8. As a result, the knockdown of Piwil2 increases the Fas protein level at the membrane. In addition to our previous finding that Piwil2 inhibits the expression of p53 through the Src/STAT3 pathway, here we demonstrate that Piwil2 represses p53 phosphorylation through p38. Our present study indicates that Piwil2 plays a role in Fas-mediated apoptosis for the first time and also can affect p53 phosphorylation in tumor cells, revealing a novel mechanism of Piwil2 in apoptosis, and supports that Piwil2 plays an active role in tumorigenesis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Citation

Siyuan Jiang, Lianfang Zhao, Yilu Lu, Meiling Wang, Yuan Chen, Dachang Tao, Yunqiang Liu, Huaqin Sun, Sizhong Zhang, Yongxin Ma. Piwil2 inhibits keratin 8 degradation through promoting p38-induced phosphorylation to resist Fas-mediated apoptosis. Molecular and cellular biology. 2014 Nov;34(21):3928-38