Open AccessPin1 and JNK1 cooperatively modulate TAp63γ
Author(s) -
Fan Xueying,
He Wei,
Hu Ke,
Chen Huimin,
Chen Li,
Fan Shijie,
Li Chenghua
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13109
Subject(s) - pin1 , transactivation , serine , phosphorylation , peptidylprolyl isomerase , transcription factor , gene isoform , prolyl isomerase , isomerase , microbiology and biotechnology , gene , biology , chemistry , biochemistry
The p63 gene encodes at least 10 isoforms, which can be classified into TA and ∆N isotypes (TAp63 and ∆Np63 proteins) according to their differences at the N termini. TAp63γ is an important transcription factor. We previously reported that peptidyl‐prolyl isomerase (PPI) Pin1 directly binds to TAp63γ protein and identified that serine 12 (S 12 ) in the transactivation domain (TAD) of TAp63γ is required for regulation of its transcriptional activity. In the present study, we report that Pin1 stimulates transcriptional and pro‐apoptotic activities of TAp63γ; this Pin1‐mediated stimulation may depend on phosphorylation of S 12 mediated by JNK1 and results in striking activation of TAp63γ. JNK1 represses transactivity of TAp63γ in cells without abundant Pin1 proteins and enhances it in the presence of sufficient levels of Pin1. Collectively, our data suggest a novel mechanism for regulation of TAp63γ transactivity: TAp63γ with unphosphorylated S 12 is moderately active, phosphorylation at this residue (pS 12 ) makes it hypoactive, and Pin1 binds to the pS 12 ‐P 13 motif and makes TAp63γ hyperactive. Our findings will aid in the elucidation of the mechanism underlying modulation of TAp63γ.