title: Quantitative nucleolar proteomics reveals nuclear re-organization during stress- induced senescence in mouse fibroblast.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, 88 Tat Chee Avenue, Hong Kong. bishnkar@cityu.edu.hk
authors.forename: Bishnupriya
authors.initials: B
authors.lastname: Kar
authors.forename: Baohua
authors.initials: B
authors.lastname: Liu
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yun W
authors.initials: YW
authors.lastname: Lam
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D007553:Isotope Labeling; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000032:analysis* / Q000378:metabolism; D000090243:Nucleophosmin; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D040901:Proteomics
chemical_list: C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D011065:Poly(ADP-ribose) Polymerases