title: Pin1 is required for the Ser727 phosphorylation-dependent Stat3 activity.
abstract: Signal transducer and activator of transcription 3 (Stat3) belongs to a family of latent cytoplasmic transcription factors important for cytokine signaling. Stat3 is constitutively activated in various tumors, and activated Stat3 itself also acts as an oncogene. Transcriptional activity of Stat3 is controlled by Tyr-phosphorylation, followed by dimerization and nuclear translocation. However, phosphorylation on Ser727 is indispensable for its maximal transcriptional activity with unclear mechanism. Here, we report that peptidyl-prolyl cis/trans isomerase 1 (Pin1), which specifically recognizes the pSer/Thr-Pro motifs on its target proteins, interacts with Stat3 upon cytokine/growth factor stimulation. Overexpression of Pin1 promotes Stat3 transcriptional activity and target gene expression, as well as recruitment of transcription coactivator, p300. These effects, however, were compromised in the Pin1-deficient cells, and were totally dependent on the Ser727 phosphorylation site. Finally, we showed that Pin1 enhances Stat3-mediated epithelial-mesenchymal transition in breast cancer cells induced by oncostatin M. Our data reveal a novel, Ser727 phosphorylation-dependent, post-translational regulation mechanism for Stat3.
authors.affiliation: Signal Transduction Laboratory, Institute of Molecular and Cell Biology, Singapore, Republic of Singapore.
authors.forename: C
authors.initials: C
authors.lastname: Lufei
authors.forename: T H
authors.initials: TH
authors.lastname: Koh
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: X
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D019556:COS Cells; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000737:chemistry / Q000235:genetics; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D050796:STAT3 Transcription Factor; D012694:Serine; D004247:DNA; D050880:p300-CBP Transcription Factors; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase