Title

Smurf2 regulates the senescence response and suppresses tumorigenesis in mice

UMMS Affiliation

Department of Cell Biology; Department of Pathology; Department of Microbiology and Physiological Systems

Date

6-1-2012

Document Type

Article

Medical Subject Headings

Ubiquitin-Protein Ligases; Cell Aging; Tumor Suppressor Proteins

Disciplines

Cancer Biology | Cell Biology

Abstract

The E3 ubiquitin ligase Smurf2 mediates ubiquitination and degradation of several protein targets involved in tumorigenesis and induces senescence in human cells. However, the functional role of Smurf2 in tumorigenesis has not been fully evaluated. In this study, we generated a mouse model of Smurf2 deficiency to characterize the function of this E3 ligase in tumorigenesis. Smurf2 deficiency attenuated p16 expression and impaired the senescence response of primary mouse embryonic fibroblasts. In support of a functional role in controlling cancer, Smurf2 deficiency increased the susceptibility of mice to spontaneous tumorigenesis, most notably B cell lymphoma. At a premalignant stage of tumorigenesis, we documented a defective senescence response in the spleens of Smurf2-deficient mice, consistent with a mechanistic link between impaired senescence regulation and increased tumorigenesis. Taken together, our findings offer the genetic evidence of an important tumor suppressor function for Smurf2.

Rights and Permissions

Citation: Ramkumar C, Kong Y, Cui H, Hao S, Jones SN, Gerstein RM, Zhang H. Smurf2 regulates the senescence response and suppresses tumorigenesis in mice. Cancer Res. 2012 Jun 1;72(11):2714-9. doi: 10.1158/0008-5472.CAN-11-3773. Link to article on publisher's website

Comments

First author Charusheila Ramkumar is a student in the Cell Biology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to article in PubMed

PubMed ID

22552287