SENP1 deSUMOylates and regulates pin1 protein activity and cellular function

Chun Hau Chen, Che Chang Chang, Tae Ho Lee, Manli Luo, Pengyu Huang, Pei Hsin Liao, Shuo Wei, Fu An Li, Ruey Hwa Chen, Xiao Zhen Zhou, Hsiu Ming Shih, Kun Ping Lu

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

The Pin1 prolyl isomerase regulates phosphorylation signaling by controlling protein conformation after phosphorylation, and its upregulation promotes oncogenesis via acting on numerous oncogenic molecules. SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in cancers. However, nothing is known about the role of SUMOylation in regulating Pin1 function. Here, we show that Pin1 is SUMOylated on Lys6 in theWWdomain and on Lys63 in the PPIase domain. Pin1 SUMOylation inhibits its protein activity and oncogenic function. We further identify that SENP1 binds to and deSUMOylates Pin1. Importantly, either overexpression of SENP1 or disruption of Pin1 SUMOylation promotes the ability of Pin1 to induce centrosome amplification and cell transformation. Moreover, SENP1 also increases Pin1 protein stability in cell cultures, and Pin1 levels are positively correlated with SENP1 levels in human breast cancer specimens. These results not only uncover Pin1 SUMOylation on Lys6/63 as a novel mechanism to inhibit its activity and function but also identify a critical role for SENP1-mediated deSUMOylation in promoting Pin1 function during tumorigenesis.

Original languageEnglish
Pages (from-to)3951-3962
Number of pages12
JournalCancer Research
Volume73
Issue number13
DOIs
Publication statusPublished - Jul 1 2013

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Chen, C. H., Chang, C. C., Lee, T. H., Luo, M., Huang, P., Liao, P. H., Wei, S., Li, F. A., Chen, R. H., Zhou, X. Z., Shih, H. M., & Lu, K. P. (2013). SENP1 deSUMOylates and regulates pin1 protein activity and cellular function. Cancer Research, 73(13), 3951-3962. https://doi.org/10.1158/0008-5472.CAN-12-4360