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Article: Quantitative nucleolar proteomics reveals nuclear re-organization during stress-induced senescence in mouse fibroblast

TitleQuantitative nucleolar proteomics reveals nuclear re-organization during stress-induced senescence in mouse fibroblast
Authors
Issue Date2011
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccellbiol/
Citation
BMC Cell Biology, 2011, v. 12, article no. 33 How to Cite?
Abstract
BACKGROUND: Nucleolus is the most prominent mammalian organelle within the nucleus which is also the site for ribosomal biogenesis. There have been many reports indicating the involvement of nucleolus in the process of aging. Several proteins related to aging have been shown to localize in the nucleolus, which suggests the role of this organelle in senescence. RESULTS: In this study, we used quantitative mass spectrometry to map the flux of proteins into and out of the nucleolus during the induction of senescence in cultured mammalian cells. Changes in the abundance of 344 nucleolar proteins in sodium butyrate-induced senescence in NIH3T3 cells were studied by SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry. Biochemically, we have validated the proteomic results and confirmed that B23 (nucleophosmin) protein was down-regulated, while poly (ADP-ribose) polymerase (PARP) and nuclear DNA helicase II (NDH II/DHX9/RHA) were up-regulated in the nucleolus upon treatment with sodium butyrate. Accumulation of chromatin in the nucleolus was also observed, by both proteomics and microscopy, in sodium butyrate-treated cells. Similar observations were found in other models of senescence, namely, in mitoxantrone- (MTX) treated cells and primary fibroblasts from the Lamin A knockout mice. CONCLUSION: Our data indicate an extensive nuclear organization during senescence and suggest that the redistribution of B23 protein and chromatin can be used as an important marker for senescence.
Persistent Identifierhttp://hdl.handle.net/10722/147636
ISSN
2013 Impact Factor: 2.844
2013 SCImago Journal Rankings: 1.605
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University Grant Council, Hong Kong160670
Research Grant Council, Hong KongHKU7655/06M
CRF HKU3/07C
Funding Information:

We would like to thank Dr. Laura Trinkle-Mulchay (Dept. Cellular & Molecular Medicine, University of Ottawa) for critically reading the manuscript. We would also like to thank members of the Yun Lam laboratory for discussions and Kenneth Lau for his technical assistance. This work was supported by the General Research Fund (GRF project number 160670) from the University Grant Council, Hong Kong, HKU7655/06M and CRF HKU3/07C from the Research Grant Council, Hong Kong.

References

 

Author Affiliations
  1. The University of Hong Kong
  2. City University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorKar, Ben_US
dc.contributor.authorLiu, Ben_US
dc.contributor.authorZhou, Zen_US
dc.contributor.authorLam, YWen_US
dc.date.accessioned2012-05-29T06:05:08Z-
dc.date.available2012-05-29T06:05:08Z-
dc.date.issued2011en_US
dc.identifier.citationBMC Cell Biology, 2011, v. 12, article no. 33en_US
dc.identifier.issn1471-2121en_US
dc.identifier.urihttp://hdl.handle.net/10722/147636-
dc.description.abstractBACKGROUND: Nucleolus is the most prominent mammalian organelle within the nucleus which is also the site for ribosomal biogenesis. There have been many reports indicating the involvement of nucleolus in the process of aging. Several proteins related to aging have been shown to localize in the nucleolus, which suggests the role of this organelle in senescence. RESULTS: In this study, we used quantitative mass spectrometry to map the flux of proteins into and out of the nucleolus during the induction of senescence in cultured mammalian cells. Changes in the abundance of 344 nucleolar proteins in sodium butyrate-induced senescence in NIH3T3 cells were studied by SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry. Biochemically, we have validated the proteomic results and confirmed that B23 (nucleophosmin) protein was down-regulated, while poly (ADP-ribose) polymerase (PARP) and nuclear DNA helicase II (NDH II/DHX9/RHA) were up-regulated in the nucleolus upon treatment with sodium butyrate. Accumulation of chromatin in the nucleolus was also observed, by both proteomics and microscopy, in sodium butyrate-treated cells. Similar observations were found in other models of senescence, namely, in mitoxantrone- (MTX) treated cells and primary fibroblasts from the Lamin A knockout mice. CONCLUSION: Our data indicate an extensive nuclear organization during senescence and suggest that the redistribution of B23 protein and chromatin can be used as an important marker for senescence.en_US
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccellbiol/en_US
dc.relation.ispartofBMC Cell Biologyen_US
dc.rightsBMC Cell Biology. Copyright © BioMed Central Ltd.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAging - metabolism-
dc.subject.meshCell Nucleolus - metabolism-
dc.subject.meshCell Nucleus - metabolism-
dc.subject.meshFibroblasts - metabolism-
dc.subject.meshNuclear Proteins - analysis - metabolism-
dc.titleQuantitative nucleolar proteomics reveals nuclear re-organization during stress-induced senescence in mouse fibroblasten_US
dc.typeArticleen_US
dc.identifier.emailKar, B: bishnkar@cityu.edu.hken_US
dc.identifier.emailLiu, B: ppliew@hku.hken_US
dc.identifier.emailZhou, Z: zhongjun@hkucc.hku.hk-
dc.identifier.authorityLiu, B=rp01485en_US
dc.identifier.authorityZhou, Z=rp00503en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1186/1471-2121-12-33en_US
dc.identifier.pmid21835027-
dc.identifier.pmcidPMC3163619-
dc.identifier.scopuseid_2-s2.0-80051504639en_US
dc.identifier.hkuros194500-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80051504639&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume12, article no. 33en_US
dc.identifier.isiWOS:000294421400001-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLam, YW=44861503800en_US
dc.identifier.scopusauthoridZhou, Z=8631856300en_US
dc.identifier.scopusauthoridLiu, B=7408693394en_US
dc.identifier.scopusauthoridKar, B=7005951511en_US
dc.identifier.citeulike9686452-

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