Smurf2 regulates the senescence response and suppresses tumorigenesis in mice.

Cancer Research
Charusheila RamkumarHong Zhang

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.

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Citations

Dec 20, 2012·Journal of the National Cancer Institute·Michael P SmithClaudia Wellbrock
Feb 6, 2014·Aging Cell·Charusheila RamkumarHong Zhang
Dec 17, 2014·Immunological Reviews·Anagh A Sahasrabuddhe, Kojo S J Elenitoba-Johnson
Jun 28, 2015·Biochimica Et Biophysica Acta·Xiao ZouMichael Blank
Apr 3, 2013·Biochimica Et Biophysica Acta·Martin Scheffner, Sharad Kumar
Sep 29, 2017·International Journal of Molecular Sciences·Michael HausmannMichael Blank
Apr 21, 2017·Oncotarget·Amrita Singh ChandhokeShirin Bonni
Aug 21, 2020·Journal of Leukocyte Biology·Tong ZhangChaohong Liu
Aug 1, 2020·Frontiers in Molecular Biosciences·Yangjinming Bai, Ying Ying
Jul 28, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sally E TrabuccoHong Zhang
Aug 18, 2018·Frontiers in Oncology·Praveen KogantiMichael Blank
Jan 21, 2017·PloS One·Afshin BeheshtiAndrew M Evens
Mar 19, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nataša IlićMichael Blank

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