PDF file - 103K, Smurf2 induces senescence in Smurf2-deficient mouse embryonic fibroblasts (MEFs). Early passage (P4) and late passage (P28) already immortalized Smurf2T/T (T/T) MEFs were stained with crystal violet and for senescence-associated beta-galactosidase (SA-beta-gal) activity following ectopic expression of Smurf2, ligase mutant C716A or GFP control
ARTICLE ABSTRACTThe 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. Cancer Res; 72(11); 2714–9. ©2012 AACR.