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

作　　者：Xinping Huang Yan Zhao Min Wei Ruipeng Zhuge Xiaofeng Zheng 

机构地区：[1]State Key Laboratory of Protein and Plant Gene Research,School of Life Sciences,Peking University,Beijing 100871,China [2]Department of Biochemistry and Molecular Biology,School of Life Sciences,Peking University,Beijing 100871,China

出　　处：《Journal of Molecular Cell Biology》2023年第2期58-71,共14页分子细胞生物学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82130081,32270756,and 81730080);the National Key Research and Development Program of China(2022YFA1302803);the Natural Science Foundation of Beijing Municipality(5212008).

摘　　要：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 discoveryof new treatment strategies for aging-related diseases. In the present study, we identified human coilin-interacting nuclear ATPaseprotein (hCINAP) as a negative regulator of aging. Depletion of cCINAP significantly shortened the lifespan of Caenorhabditiselegans and accelerated primary cell aging. Moreover, mCINAP deletion markedly promoted organismal aging and stimulatedsenescence-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 decreasesp53 stability by attenuating the interaction between p14ARF and MDM2;on the other hand, hCINAP promotes MDM2 transcriptionvia 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 underlyingthe aging process.

关 键 词：hCINAP HDAC1/CoREST complex P14ARF MDM2 transcription SENESCENCE 

分 类 号：Q2[生物学—细胞生物学]