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hCINAP alleviates senescence by regulating MDM2 via p14ARF and the HDAC1/CoREST complex

Cellular senescence is a major process affected by multiple signals and coordinated by a complex signal response network. Identification of novel regulators of cellular senescence and elucidation of their molecular mechanisms will aid in the discovery of new treatment strategies for aging-related di...

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Detalles Bibliográficos
Autores principales: Huang, Xinping, Zhao, Yan, Wei, Min, Zhuge, Ruipeng, Zheng, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476552/
https://www.ncbi.nlm.nih.gov/pubmed/36881716
http://dx.doi.org/10.1093/jmcb/mjad015
Descripción
Sumario:Cellular senescence is a major process affected by multiple signals and coordinated by a complex signal response network. Identification of novel regulators of cellular senescence and elucidation of their molecular mechanisms will aid in the discovery of new treatment strategies for aging-related diseases. In the present study, we identified human coilin-interacting nuclear ATPase protein (hCINAP) as a negative regulator of aging. Depletion of cCINAP significantly shortened the lifespan of Caenorhabditis elegans and accelerated primary cell aging. Moreover, mCINAP deletion markedly promoted organismal aging and stimulated senescence-associated secretory phenotype in the skeletal muscle and liver from mouse models of radiation-induced senescence. Mechanistically, hCINAP functions through regulating MDM2 status by distinct mechanisms. On the one hand, hCINAP decreases p53 stability by attenuating the interaction between p14ARF and MDM2; on the other hand, hCINAP promotes MDM2 transcription via inhibiting the deacetylation of H3K9ac in the MDM2 promoter by hindering the HDAC1/CoREST complex integrity. Collectively, our data demonstrate that hCINAP is a negative regulator of aging and provide insight into the molecular mechanisms underlying the aging process.