Email updates

Keep up to date with the latest news and content from BMC Cell Biology and BioMed Central.

Open Access Highly Accessed Research article

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

Bishnupriya kar1*, Baohua Liu2, Zhongjun Zhou2 and Yun W Lam1

Author Affiliations

1 Department of Biology and Chemistry, City University of Hong Kong, 88 Tat Chee Avenue, Hong Kong

2 Department of Biochemistry, The University of Hong Kong, 21 Sassoon Road, Hong Kong

For all author emails, please log on.

BMC Cell Biology 2011, 12:33  doi:10.1186/1471-2121-12-33

Published: 11 August 2011

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.