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ZNF746/PARIS overexpression induces cellular senescence through FoxO1/p21 axis activation in myoblasts

Title
ZNF746/PARIS overexpression induces cellular senescence through FoxO1/p21 axis activation in myoblasts
Authors
Bae, Ju-HyeonJeong, Hyeon-JuKim, HyebeenLeem, Young-EunRyu, DongryeolPark, Sang ChulLee, Yun-IlCho, Sung ChunKang, Jong-Sun
DGIST Authors
Lee, Yun-Il
Issue Date
2020-05
Citation
Cell Death and Disease, 11(5), 359
Type
Article
Article Type
Article
Keywords
NECROSIS-FACTOR-ALPHATRANSCRIPTION FACTORSSTEM-CELLSMUSCLENEURODEGENERATION
ISSN
2041-4889
Abstract
Various stresses, including oxidative stress, impair the proliferative capacity of muscle stem cells leading to declined muscle regeneration related to aging or muscle diseases. ZNF746 (PARIS) is originally identified as a substrate of E3 ligase Parkin and its accumulation is associated with Parkinson’s disease. In this study, we investigated the role of PARIS in myoblast function. PARIS is expressed in myoblasts and decreased during differentiation. PARIS overexpression decreased both proliferation and differentiation of myoblasts without inducing cell death, whereas PARIS depletion enhanced myoblast differentiation. Interestingly, high levels of PARIS in myoblasts or fibroblasts induced cellular senescence with alterations in gene expression associated with p53 signaling, inflammation, and response to oxidative stress. PARIS overexpression in myoblasts starkly enhanced oxidative stress and the treatment of an antioxidant Trolox attenuated the impaired proliferation caused by PARIS overexpression. FoxO1 and p53 proteins are elevated in PARIS-overexpressing cells leading to p21 induction and the depletion of FoxO1 or p53 reduced p21 levels induced by PARIS overexpression. Furthermore, both PARIS and FoxO1 were recruited to p21 promoter region and Trolox treatment attenuated FoxO1 recruitment. Taken together, PARIS upregulation causes oxidative stress-related FoxO1 and p53 activation leading to p21 induction and cellular senescence of myoblasts. © 2020, The Author(s).
URI
http://hdl.handle.net/20.500.11750/12054
DOI
10.1038/s41419-020-2552-7
Publisher
Nature Publishing Group
Related Researcher
Files:
There are no files associated with this item.
Collection:
Division of Biotechnology1. Journal Articles


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