Piwil2 suppresses p53 by inducing phosphorylation of signal transducer and activator of transcription 3 in tumor cells.
Piwi proteins have been implicated in germ cell proliferation, differentiation, germline stem cell maintenance and transposon control in germline from Drosophila to mammals. The Piwi-like2 (piwil2) gene is mainly expressed in testis or embryonic cells among normal tissues but widely expressed in tumors. However, it remains to be fully determined through which mechanism piwil2 is involved in tumorigenesis. Here we report that Human piwil2, or Hili represses the tumor suppressor P53 in human cancer cells. Immunoprecipitation analysis shows that Piwil2 can directly associate with Signal Transducer and Activator of Transcription 3 (STAT3) protein via its PAZ domain and form a Piwil2/STAT3/c-Src triple protein-protein complex. Furthermore, STAT3 is phosphorylated by c-Src and translocated to nucleus, then binds to P53 promoter and represses its transcription. The present study demonstrated that Piwil2 plays a role in anti-apoptosis in tumor cells possessing P53 as a positive regulator of STAT3 signaling pathway, providing novel sights into roles of Piwil2 in tumorigenesis.
State Key Laboratory of Biotherapy, Division of Morbid Genomics, Department of Medical Genetics, West China Hospital, Sichuan University, Chengdu, China.
Yilu
Y
Lu
Kun
K
Zhang
Chao
C
Li
Youlin
Y
Yao
Dachang
D
Tao
Yunqiang
Y
Liu
Sizong
S
Zhang
Yongxin
Y
Ma
D017209:Apoptosis; D060565:Argonaute Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D060565:Argonaute Proteins; C486868:PIWIL2 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016159:Tumor Suppressor Protein p53; D019061:src-Family Kinases