SUMO protease SENP1 deSUMOylates and stabilizes c-Myc

Xiao Xin Suna, Yingxiao Chena, Yulong Sua, Xiaoyan Wanga, Krishna Mohan Chauhana, Juan Lianga, Colin J. Daniela, Rosalie C. Searsa, Mu Shui Daia

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Posttranslationalmodifications play a crucial role in the proper control of c-Myc protein stability and activity. c-Myc can be modified by small ubiquitin-like modifier (SUMO). However, how SUMOylation regulates c-Myc stability and activity remains to be elucidated. The deSUMOylation enzyme, SENP1, has recently been shown to have a prooncogenic role in cancer; however, mechanistic understanding of this is limited. Here we show that SENP1 is a c-Myc deSUMOylating enzyme. SENP1 interacts with and deSUMOylates c-Myc in cells and in vitro. Overexpression of wild-type SENP1, but not its catalytically inactive C603S mutant, markedly stabilizes c-Myc and increases its levels and activity. Knockdown of SENP1 reduces c-Myc levels, induces cell cycle arrest, and drastically suppresses cell proliferation. We further show that c-Myc can be comodified by both ubiquitination and SUMOylation. SENP1-mediated deSUMOylation reduces c-Myc polyubiquitination, suggesting that SUMOylation promotes c-Myc degradation through the proteasome system. Interestingly, SENP1- mediated deSUMOylation promotes the accumulation of monoubiquitinated c-Myc and its phosphorylation at serine 62 and threonine 58. SENP1 is frequently overexpressed, correlating with the high expression of c-Myc, in breast cancer tissues. Together, these results reveal that SENP1 is a crucial c-Myc deSUMOylating enzyme that positively regulates c-Myc's stability and activity.

Original languageEnglish (US)
Pages (from-to)10983-10988
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number43
DOIs
StatePublished - Oct 23 2018

Keywords

  • C-Myc
  • DeSUMOylation
  • SENP1
  • SUMOylation
  • Ubiquitination

ASJC Scopus subject areas

  • General

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