Related Experiment Video

Updated: May 4, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation

Zhenghong Lin1, Heeyoung Yang1, Can Tan1

  • 1Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.

Cell Reports
|December 17, 2013
PubMed

Insights

The tumor suppressor USP10 protects SIRT6 from degradation, inhibiting cancer growth. Reduced USP10 and SIRT6 levels in colon cancers indicate their crucial role in preventing tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Oncology

Background:

  • Reduced expression of the SIRT6 tumor suppressor is linked to tumorigenesis.
  • The mechanisms causing SIRT6 protein downregulation in human cancers are not fully understood.

Purpose of the Study:

  • To identify molecular mechanisms behind SIRT6 downregulation in cancer.
  • To investigate the interaction between USP10 and SIRT6 in cancer regulation.

Main Methods:

  • Proteomic approach to identify SIRT6-interacting proteins.
  • Assays to determine USP10's effect on SIRT6 ubiquitination and degradation.
  • Analysis of USP10 and SIRT6 protein levels in human colon cancer tissues.

Main Results:

  • USP10 was identified as a SIRT6-interacting protein.
  • USP10 suppresses SIRT6 ubiquitination, preventing its proteasomal degradation.
  • USP10, via SIRT6 and p53, inhibits cell-cycle progression, cancer growth, and tumor formation.
  • Significant reductions in both USP10 and SIRT6 protein expression were observed in human colon cancers.

Conclusions:

  • USP10 and SIRT6 are tumor suppressors that interact to regulate cell-cycle progression and proliferation.
  • Dysregulation of USP10 promotes tumorigenesis by increasing SIRT6 degradation.
  • This study reveals a crosstalk between USP10 and SIRT6 in cancer development.

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