Pin1 is required for the Ser727 phosphorylation-dependent Stat3 activity

Lufei, C; Koh, T H; Uchida, T; Cao, X

doi:10.1038/sj.onc.1210567

Cited by 106Cytokine Signaling Pathways and InteractionsSignaling Pathways in DiseaseProtein Tyrosine Phosphatases

Pin1 is required for the Ser727 phosphorylation-dependent Stat3 activity

Lufei, C, Koh, T H, Uchida, T, Cao, X·2007·Oncogene

DOI 10.1038/sj.onc.1210567

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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.

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Pin1 regulates the functions of transcription factors NFAT, STAT3, and NF-κB that play important roles in the immune system.
“It has been reported that Pin1 regulates the functions of transcription factors, such as NFAT [2], STAT3 [3], and NF-κB [4] that play important roles in the immune system.”
From Prolyl Isomerase Pin1 Protects Mice from Endotoxin Shock (2011) · cites this paper as [3]

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“Tyr-phosphorylation of Stat3 leads to dimerization via reciprocal interaction between the SH2 domain and the phosphorylated Tyr705, then nuclear transport, DNA binding and regulation of target gene expression (Darnell et al., 1994).”
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Summary
Wen, Z., Zhong, Z., & Darnell, J. E., Jr. (2013)
Phospho-Ser727 of STAT3 regulates STAT3 activity by enhancing dephosphorylation of phospho-Tyr705 largely through TC45
Wakahara, R., Kunimoto, H., Tanino, K., Kojima, H., Inoue, A., Shintaku, H., & Nakajima, K. (2012) · Genes to Cells · doi:10.1111/j.1365-2443.2011.01575.x · Cited by 95 · see citing works

Authors: Lufei, C., Koh, T. H., Uchida, T., & Cao, X.
Affiliations: Institute of Molecular and Cell Biology (SG)
Tohoku University (JP)
Corresponding author: Cao, X
ORCID: Uchida, T
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2007-06-11
Volume: 26
Issue: 55
Pages: 7656-7664
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1210567
OpenAlex: W1994638410
Cited by: 106
References: 33
Citations by year: 2026: 2 · 2025: 2 · 2024: 6 · 2023: 2 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 9 · 2013: 11 · 2012: 5
FWCI: 4.05
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Funders: National University of Singapore
Topics: Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords: STAT3, Pin1, peptidyl-prolyl isomerase, post-translational regulation, P300, transcriptional activation, cytokine signaling, epithelial-mesenchymal transition, oncostatin M, breast cancer
MeSH terms: NIMA-Interacting Peptidylprolyl Isomerase, Animals, Chlorocebus aethiops, DNA, HeLa Cells, Humans, Phosphorylation, Serine, Transcription, Genetic, COS Cells, Peptidylprolyl Isomerase, Cell Proliferation, STAT3 Transcription Factor, p300-CBP Transcription Factors

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Pin1 is required for the Ser727 phosphorylation-dependent Stat3 activity

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