Article: Quantitative nucleolar proteomics reveals nuclear re-organization during stress-induced senescence in mouse fibroblast
| Title | Quantitative nucleolar proteomics reveals nuclear re-organization during stress-induced senescence in mouse fibroblast | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Kar, B2 Liu, B1 Zhou, Z1 Lam, YW2 | ||||||
| Issue Date | 2011 | ||||||
| Publisher | BioMed 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?] DOI: http://dx.doi.org/10.1186/1471-2121-12-33 | ||||||
| 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. | ||||||
| ISSN | 1471-2121 2011 Impact Factor: 2.589 2011 SCImago Journal Rankings: 0.399 | ||||||
| DOI | http://dx.doi.org/10.1186/1471-2121-12-33 | ||||||
| ISI Accession Number ID | WOS:000294421400001
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. | ||||||
| PubMed Central ID | PMC3163619 | ||||||
| References | References in Scopus |
| dc.contributor.author | Kar, B | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Liu, B | ||||||
| dc.contributor.author | Zhou, Z | ||||||
| dc.contributor.author | Lam, YW | ||||||
| dc.date.accessioned | 2012-05-29T06:05:08Z | ||||||
| dc.date.available | 2012-05-29T06:05:08Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.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. | ||||||
| dc.description.nature | published_or_final_version | ||||||
| dc.identifier.citation | BMC Cell Biology, 2011, v. 12, article no. 33 [How to Cite?] DOI: http://dx.doi.org/10.1186/1471-2121-12-33 | ||||||
| dc.identifier.citeulike | 9686452 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1186/1471-2121-12-33 | ||||||
| dc.identifier.hkuros | 194500 | ||||||
| dc.identifier.isi | WOS:000294421400001
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. | ||||||
| dc.identifier.issn | 1471-2121 2011 Impact Factor: 2.589 2011 SCImago Journal Rankings: 0.399 | ||||||
| dc.identifier.pmcid | PMC3163619 | ||||||
| dc.identifier.pmid | 21835027 | ||||||
| dc.identifier.scopus | eid_2-s2.0-80051504639 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/147636 | ||||||
| dc.identifier.volume | 12, article no. 33 | ||||||
| dc.language | eng | ||||||
| dc.publisher | BioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccellbiol/ | ||||||
| dc.publisher.place | United Kingdom | ||||||
| dc.relation.ispartof | BMC Cell Biology | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | BMC Cell Biology. Copyright © BioMed Central Ltd. | ||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||
| dc.subject.mesh | Aging - metabolism | ||||||
| dc.subject.mesh | Cell Nucleolus - metabolism | ||||||
| dc.subject.mesh | Cell Nucleus - metabolism | ||||||
| dc.subject.mesh | Fibroblasts - metabolism | ||||||
| dc.subject.mesh | Nuclear Proteins - analysis - metabolism | ||||||
| dc.title | Quantitative nucleolar proteomics reveals nuclear re-organization during stress-induced senescence in mouse fibroblast | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- City University of Hong Kong