USP10 Antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation

Zhenghong Lin, Heeyoung Yang, Can Tan, Jinping Li, Zhaojian Liu, Qiu Quan, Sinyi Kong, Junsheng Ye, Beixue Gao, Deyu Fang*

*Corresponding author for this work

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell-cycle progression, cancer cell growth, and tumor formation. To support this conclusion, we detected significant reductions in both USP10 and SIRT6 protein expression in human colon cancers. Our study discovered crosstalk between two tumor-suppressive genes in regulating cell-cycle progression and proliferation and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6 degradation.

Original languageEnglish (US)
Pages (from-to)1639-1649
Number of pages11
JournalCell reports
Volume5
Issue number6
DOIs
StatePublished - Dec 26 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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