Disruption of nucleocytoplasmic trafficking as a cellular senescence driver

Cited 2 time in scopus
Metadata Downloads
Title
Disruption of nucleocytoplasmic trafficking as a cellular senescence driver
Author(s)
Ji Hwan Park; S J Ryu; B J Kim; H J Cho; C H Park; H J C Choi; E J Jang; E J Yang; J A Hwang; S H Woo; J H Lee; J H Park; K M Choi; Y Y Kwon; C K Lee; J T Park; S C Cho; Y I Lee; S B Lee; J A Han; K A Cho; M S Kim; D Hwang; Y S Lee; S C Park
Bibliographic Citation
Experimental and Molecular Medicine, vol. 53, no. 6, pp. 1092-1108
Publication Year
2021
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.
ISSN
1226-3613
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s12276-021-00643-6
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.