title: Smurf2 regulates the senescence response and suppresses tumorigenesis in mice.
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.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Charusheila
authors.initials: C
authors.lastname: Ramkumar
authors.forename: Yahui
authors.initials: Y
authors.lastname: Kong
authors.forename: Hang
authors.initials: H
authors.lastname: Cui
authors.forename: Suyang
authors.initials: S
authors.lastname: Hao
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Jones
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Gerstein
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000375:Aging; D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D051798:Inhibitor of Differentiation Protein 1 / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000502:physiology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D025521:Tumor Suppressor Proteins; C533325:Smurf2 protein, mouse; D044767:Ubiquitin-Protein Ligases