Comprehensive analysis of the ubiquitinome during oncogene-induced senescence in human fibroblasts

Cell Cycle
Fee BengschRugang Zhang

Abstract

Oncogene-induced senescence (OIS) is an important tumor suppression mechanism preventing uncontrolled proliferation in response to aberrant oncogenic signaling. The profound functional and morphological remodelling of the senescent cell involves extensive changes. In particular, alterations in protein ubiquitination during senescence have not been systematically analyzed previously. Here, we report the first global ubiquitination profile of primary human cells undergoing senescence. We employed a well-characterized in vitro model of OIS, primary human fibroblasts expressing oncogenic RAS. To compare the ubiquitinome of RAS-induced OIS and controls, ubiquitinated peptides were enriched by immune affinity purification and subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS). We identified 4,472 ubiquitination sites, with 397 sites significantly changed (>3 standard deviations) in senescent cells. In addition, we performed mass spectrometry analysis of total proteins in OIS and control cells to account for parallel changes in both protein abundance and ubiquitin levels that did not affect the percentage of ubiquitination of a given protein. Pathway analysis revealed that the OIS-induced ubiquitinome alterations m...Continue Reading

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Citations

Jun 16, 2016·Cell Metabolism·Christopher D Wiley, Judith Campisi
Nov 17, 2017·Clinical and Experimental Pharmacology & Physiology·Dongsheng ShangZhigang Tu
Jun 27, 2019·Current Medicinal Chemistry·Maria Hernandez-ValladaresAstrid Guldbrandsen
Aug 30, 2017·Frontiers in Molecular Neuroscience·Mylène HervéEl Chérif Ibrahim
Apr 25, 2020·Frontiers in Molecular Biosciences·Boris Negrutskii
Oct 21, 2020·Molecular and Cellular Biology·Matthew J PayeaMyriam Gorospe
Mar 7, 2017·Analytical Chemistry·Albert CasanovasJoaquin Abian

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Methods Mentioned

BETA
ubiquitination
affinity purification
protein assay
acetylation

Software Mentioned

MaxQuant
QIAGEN Pathway Analysis
IPA

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