Quantitative proteomic analysis of cellular senescence: from systems biology to targeted signaling pathways
type: CreativeWork
description: Cellular senescence, an irreversible cell cycle arrest induced by a diversity of stimuli, has been considered as an innate tumor suppressing mechanism with implications and applications in cancer therapy. The senescence phenomenon was first associated with aging as Hayflick and colleagues observed that normal human fibroblasts lost their proliferative capacity after a finite number of cell divisions in cell culture. Oncogene activation acting to potentiate or overstimulate normal growth signaling is a hallmark of cancer. However, in “normal” cells oncogene activation does not lead to transformation, but instead provokes cellular senescence. One characteristic feature of the oncogene induced senescence phenotypes involves formation of a unique type of chromatin, known as senescence associated heterochromatin foci. Histone modifications have been shown to be part of this chromatin formation. With new mass spectrometric technologies developed to analyze histone modifications, specifically acetylation and methylation, global histone modification changes in senescent cells were studied extensively. A top down proteomic approach to profile all core histones was developed and applied to study histone acetylation changes after selective knocking down or inhibition of histone deacetylases. This method also allowed us to find decreased acetylation levels on all core histone proteins in senescent cells. An alternative method analyzing peptides generated by protease digestion provided a quantitative view of most of the methylation sites on histone H3. The changed pattern of methylation on Lys 27 and Lys 36 of histone H3 in senescent cells, along with hypoacetylation on all core histones, were consistent with chromatin in senescent cells adapting a more compact, heterochromatic state. The global formation of heterochromatin did not translate to globally suppressed levels of transcription and protein translation. A comprehensive quantitative proteomic study applying SILAC (stable…
abstract: Cellular senescence, an irreversible cell cycle arrest induced by a diversity of stimuli, has been considered as an innate tumor suppressing mechanism with implications and applications in cancer therapy. The senescence phenomenon was first associated with aging as Hayflick and colleagues observed that normal human fibroblasts lost their proliferative capacity after a finite number of cell divisions in cell culture. Oncogene activation acting to potentiate or overstimulate normal growth signaling is a hallmark of cancer. However, in “normal” cells oncogene activation does not lead to transformation, but instead provokes cellular senescence. One characteristic feature of the oncogene induced senescence phenotypes involves formation of a unique type of chromatin, known as senescence associated heterochromatin foci. Histone modifications have been shown to be part of this chromatin formation. With new mass spectrometric technologies developed to analyze histone modifications, specifically acetylation and methylation, global histone modification changes in senescent cells were studied extensively. A top down proteomic approach to profile all core histones was developed and applied to study histone acetylation changes after selective knocking down or inhibition of histone deacetylases. This method also allowed us to find decreased acetylation levels on all core histone proteins in senescent cells. An alternative method analyzing peptides generated by protease digestion provided a quantitative view of most of the methylation sites on histone H3. The changed pattern of methylation on Lys 27 and Lys 36 of histone H3 in senescent cells, along with hypoacetylation on all core histones, were consistent with chromatin in senescent cells adapting a more compact, heterochromatic state. The global formation of heterochromatin did not translate to globally suppressed levels of transcription and protein translation. A comprehensive quantitative proteomic study applying SILAC (stable…
author: Li, Mingxi
language: en
keywords: quantitative proteomics, cellular senescence, histone modifications
date published: 2011-12
date modified: 2026-07-22T22:25:27Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/29510