HCINAP Alleviates Senescence by Regulating MDM2 Via P14ARF and the HDAC1/CoREST Complex

Overview

Journal J Mol Cell Biol

Publisher Oxford University Press

Specialty Molecular Biology

Date 2023 Mar 7

PMID 36881716

Authors

Xinping Huang

Yan Zhao

Min Wei

Ruipeng Zhuge

Xiaofeng Zheng

Affiliations

Soon will be listed here.

Abstract

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.

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PMID: 38438773 PMC: 10912136. DOI: 10.1007/s11033-024-09247-5.

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