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Disruption of nucleocytoplasmic trafficking as a cellular senescence driver

Title
Disruption of nucleocytoplasmic trafficking as a cellular senescence driver
Authors
Park, Ji-HwanRyu, Sung JinKim, Byung JuCho, Hyun-JiPark, Chi HyunChoi, Hyo Jei ClaudiaJang, Eun JinYang, Eun JaeHwang, Jeong-AWoo, Seung HwaLee, Jun HyungPark, Ji HwanChoi, Kyung-MiKwon, Young-YonLee, Cheol-KooPark, Joon TaeCho, Sung ChunLee, Yun-IlLee, Sung BaeHan, Jeong A.Cho, Kyung A.Kim, Min-SikHwang, DaeheeLee, Young-SamPark, Sang Chul
DGIST Authors
Park, Ji-Hwan; Ryu, Sung Jin; Kim, Byung Ju; Cho, Hyun-Ji; Park, Chi Hyun; Choi, Hyo Jei Claudia; Jang, Eun Jin; Yang, Eun Jae; Hwang, Jeong-A; Woo, Seung Hwa; Lee, Jun Hyung; Park, Ji Hwan; Choi, Kyung-Mi; Kwon, Young-Yon; Lee, Cheol-Koo; Park, Joon Tae; Cho, Sung Chun; Lee, Yun-IlLee, Sung Bae; Han, Jeong A.; Cho, Kyung A.; Kim, Min-Sik; Hwang, Daehee; Lee, Young-Sam; Park, Sang Chul
Issue Date
2021-06
Citation
Experimental and Molecular Medicine, 53(6), 1092-1108
Type
Article
Keywords
APOPTOSISCELLSEXPRESSIONIDENTIFICATIONCLEARANCEINDUCED PREMATURE SENESCENCETRANSCRIPTION FACTOR SP1REPLICATIVE SENESCENCEDOWN-REGULATIONSTRESS
ISSN
1226-3613
Abstract
Senescent cells exhibit a reduced response to intrinsic and extrinsic stimuli. This diminished reaction may be explained by the disrupted transmission of nuclear signals. However, this hypothesis requires more evidence before it can be accepted as a mechanism of cellular senescence. A proteomic analysis of the cytoplasmic and nuclear fractions obtained from young and senescent cells revealed disruption of nucleocytoplasmic trafficking (NCT) as an essential feature of replicative senescence (RS) at the global level. Blocking NCT either chemically or genetically induced the acquisition of an RS-like senescence phenotype, named nuclear barrier-induced senescence (NBIS). A transcriptome analysis revealed that, among various types of cellular senescence, NBIS exhibited a gene expression pattern most similar to that of RS. Core proteomic and transcriptomic patterns common to both RS and NBIS included upregulation of the endocytosis-lysosome network and downregulation of NCT in senescent cells, patterns also observed in an aging yeast model. These results imply coordinated aging-dependent reduction in the transmission of extrinsic signals to the nucleus and in the nucleus-to-cytoplasm supply of proteins/RNAs. We further showed that the aging-associated decrease in Sp1 transcription factor expression was critical for the downregulation of NCT. Our results suggest that NBIS is a modality of cellular senescence that may represent the nature of physiological aging in eukaryotes. © 2021, The Author(s).
URI
http://hdl.handle.net/20.500.11750/14009
DOI
10.1038/s12276-021-00643-6
Publisher
Springer Nature
Related Researcher
Files:
Collection:
Division of Biotechnology1. Journal Articles
Well Aging Research Center1. Journal Articles
Department of Brain SciencesLaboratory of Neurodegenerative Diseases and Aging1. Journal Articles
Department of New BiologyLaboratory for QBIO and Precision Medicine1. Journal Articles
Department of New BiologySenescence-Associated Mechanism Lab1. Journal Articles


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