Smurf2 regulates the senescence response and suppresses tumorigenesis in mice
Authors
Ramkumar, CharusheilaKong, Yahui
Cui, Hang
Hao, Suyang
Jones, Stephen N.
Gerstein, Rachel M.
Zhang, Hong
UMass Chan Affiliations
Department of Microbiology and Physiological SystemsDepartment of Pathology
Department of Cell Biology
Document Type
Journal ArticlePublication Date
2012-06-01
Metadata
Show full item recordAbstract
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.Source
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 websiteDOI
10.1158/0008-5472.CAN-11-3773Permanent Link to this Item
http://hdl.handle.net/20.500.14038/51100PubMed ID
22552287Notes
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 PubMedae974a485f413a2113503eed53cd6c53
10.1158/0008-5472.CAN-11-3773