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

BMC Cell Biology

Research Article

Zhongjun Zhou¹  Baohua Liu¹  Bishnupriya kar²  Yun W Lam² 

[1] Department of Biochemistry, The University of Hong Kong, 21 Sassoon Road, Hong Kong;Department of Biology and Chemistry, City University of Hong Kong, 88 Tat Chee Avenue, Hong Kong;

关键词: NIH3T3 Cell;    Senescent Cell;    Sodium Butyrate;    Ribosomal Biogenesis;    Nucleolar Protein;   

DOI  :  10.1186/1471-2121-12-33

 received in 2011-01-25, accepted in 2011-08-11,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundNucleolus 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.ResultsIn 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.ConclusionOur 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.

【 授权许可】

CC BY   
© kar et al; licensee BioMed Central Ltd. 2011