Proteasome Activity Influences UV-mediated Subnuclear Localization Changes of NPM
Overview
Affiliations
UV damage activates cellular stress signaling pathways, causes DNA helix distortions and inhibits transcription by RNA polymerases I and II. In particular, the nucleolus, which is the site of RNA polymerase I transcription and ribosome biogenesis, disintegrates following UV damage. The disintegration is characterized by reorganization of the subnucleolar structures and change of localization of many nucleolar proteins. Here we have queried the basis of localization change of nucleophosmin (NPM), a nucleolar granular component protein, which is increasingly detected in the nucleoplasm following UV radiation. Using photobleaching experiments of NPM-fluorescent fusion protein in live human cells we show that NPM mobility increases after UV damage. However, we show that the increase in NPM nucleoplasmic abundance after UV is independent of UV-activated cellular stress and DNA damage signaling pathways. Unexpectedly, we find that proteasome activity affects NPM redistribution. NPM nucleolar expression was maintained when the UV-treated cells were exposed to proteasome inhibitors or when the expression of proteasome subunits was inhibited using RNAi. However, there was no evidence of increased NPM turnover in the UV damaged cells, or that ubiquitin or ubiquitin recycling affected NPM localization. These findings suggest that proteasome activity couples to nucleolar protein localizations in UV damage stress.
Nucleolar dynamics are determined by the ordered assembly of the ribosome.
Sheu-Gruttadauria J, Yan X, Stuurman N, Vale R, Floor S bioRxiv. 2023; .
PMID: 37808656 PMC: 10557630. DOI: 10.1101/2023.09.26.559432.
Structure-guided paradigm shifts in flavivirus assembly and maturation mechanisms.
Nicholls C, Sevvana M, Kuhn R Adv Virus Res. 2021; 108:33-83.
PMID: 33837721 PMC: 7510438. DOI: 10.1016/bs.aivir.2020.08.003.
Russo L, Ferruzo P, Forti F Front Cell Dev Biol. 2021; 9:624933.
PMID: 33777934 PMC: 7991746. DOI: 10.3389/fcell.2021.624933.
Lin P, Mobasher M, Hakakian Y, Kakarla V, Naseem A, Ziai H Histochem Cell Biol. 2015; 144(6):543-58.
PMID: 26265134 PMC: 5662186. DOI: 10.1007/s00418-015-1359-6.
Pentecost M, Vashisht A, Lester T, Voros T, Beaty S, Park A PLoS Pathog. 2015; 11(3):e1004739.
PMID: 25782006 PMC: 4363627. DOI: 10.1371/journal.ppat.1004739.