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Multi-omic data integration links deleted in breast cancer 1 (DBC1) degradation to chromatin remodeling in inflammatory response.

Authors :
Nakayasu ES
Brown RN
Ansong C
Sydor MA
Imtiaz S
Mihai C
Sontag R
Hixson KK
Monroe ME
Sobreira TJ
Orr G
Petyuk VA
Yang F
Smith RD
Adkins JN
Source :
Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2013 Aug; Vol. 12 (8), pp. 2136-47. Date of Electronic Publication: 2013 May 02.
Publication Year :
2013

Abstract

This study investigated the dynamics of ubiquitinated proteins after the inflammatory stimulation of RAW 264.7 macrophage-like cells with bacterial lipopolysaccharide. Ubiquitination is a common protein post-translational modification that regulates many key cellular functions. We demonstrated that levels of global ubiquitination and K48 and K63 polyubiquitin chains change after lipopolysaccharide stimulation. Quantitative proteomic analysis identified 1199 ubiquitinated proteins, 78 of which exhibited significant changes in ubiquitination levels following stimulation. Integrating the ubiquitinome data with global proteomic and transcriptomic results allowed us to identify a subset of 88 proteins that were targeted for degradation after lipopolysaccharide stimulation. Using cellular assays and Western blot analyses, we biochemically validated DBC1 (a histone deacetylase inhibitor) as a degradation substrate that is targeted via an orchestrated mechanism utilizing caspases and the proteasome. The degradation of DBC1 releases histone deacetylase activity, linking lipopolysaccharide activation to chromatin remodeling in caspase- and proteasome-mediated signaling.

Details

Language :
English
ISSN :
1535-9484
Volume :
12
Issue :
8
Database :
MEDLINE
Journal :
Molecular & cellular proteomics : MCP
Publication Type :
Academic Journal
Accession number :
23639857
Full Text :
https://doi.org/10.1074/mcp.M112.026138