Aging Cell | |
let‐7‐repressesed Shc translation delays replicative senescence | |
Fang Xu1  Lijun Pang1  Xiaoyu Cai1  Xinwen Liu1  Shuai Yuan1  Xiuqin Fan1  Bin Jiang1  Xiaowei Zhang1  Yali Dou2  Myriam Gorospe3  | |
[1] Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China;Department of Pathology and Biological Chemistry, University of Michigan, Ann Arbor, MI, USA;Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA | |
关键词: cellular lifespan; let‐7a; p66Shc; replicative senescence; translational regulation; | |
DOI : 10.1111/acel.12176 | |
来源: Wiley | |
【 摘 要 】
The p66Shc adaptor protein is an important regulator of lifespan in mammals, but the mechanisms responsible are still unclear. Here, we show that expression of p66Shc, p52Shc, and p46Shc is regulated at the post-transcriptional level by the microRNA let-7a. The levels of let-7a correlated inversely with the levels of Shc proteins without affecting Shc mRNA levels. We identified ‘seedless’ let-7a interaction elements in the coding region of Shc mRNA; mutation of the ‘seedless’ interaction sites abolished the regulation of Shc by let-7a. Our results further revealed that repression of Shc expression by let-7a delays senescence of human diploid fibroblasts (HDFs). In sum, our findings link let-7a abundance to the expression of p66Shc, which in turn controls the replicative lifespan of HDFs.Summary
【 授权许可】
CC BY
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
【 预 览 】
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