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PMID: 18515799 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Physical and functional interactions of monoubiquitylated transactivators with the proteasome.

The Journal of biological chemistry ·Vol. 283 ·No. 31 ·2008-08-01 ·Pages 21789-98

Archer CT, Burdine L, Liu B, Ferdous A, Johnston SA, Kodadek T

Abstract

Destabilization of activator-DNA complexes by the proteasomal ATPases can inhibit transcription by limiting activator interaction with DNA. Modification of the activator by monoubiquitylation protects the activator from this destabilization activity. In this study, we probe the mechanism of this protective effect of monoubiquitylation. Using novel label transfer and chemical cross-linking techniques, we show that ubiquitin contacts the ATPase complex directly, apparently via Rpn1 and Rpt1. This interaction results in the dissociation of the activation domain-ATPase complex via an allosteric process. A model is proposed in which activator monoubiquitylation serves to limit the lifetime of the activator-ATPase complex interaction and thus the ability of the ATPases to unfold the activator and dissociate the protein-DNA complex.

MeSH Terms
Adenosine Triphosphatases/chemistry,metabolism Cross-Linking Reagents/pharmacology DNA/chemistry DNA-Binding Proteins/metabolism HeLa Cells Humans Hydrolysis Inhibitory Concentration 50 Models, Chemical Proteasome Endopeptidase Complex/chemistry Protein Binding Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/metabolism Transcriptional Activation Ubiquitin/chemistry
Chemicals
Cross-Linking Reagents DNA-Binding Proteins RPN1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Ubiquitin DNA Proteasome Endopeptidase Complex Adenosine Triphosphatases RPT1 protein, S cerevisiae
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Archer Chase T
Division of Translational Research and Department of Internal Medicine, University of Texas-Southwestern Medical Center, Dallas, TX 75390-9185, USA.
Burdine Lyle
Liu Bo
Ferdous Anwarul
Johnston Stephen Albert
Kodadek Thomas
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
Published
2008-08-01
Epub
2008-00-30
Pages
21789-98
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2490782
Subset
IM
Grants
NIGMS NIH HHS · GM 71833 · United States
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