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PMID: 17167105 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The role of the proteasomal ATPases and activator monoubiquitylation in regulating Gal4 binding to promoters.

Genes & development ·Vol. 21 ·No. 1 ·2007-01-01 ·Pages 112-23

Ferdous A, Sikder D, Gillette T, Nalley K, Kodadek T, Johnston SA

Abstract

Recent studies have shown that the intersection between transcription and proteins involved in the ubiquitin-proteasome pathway encompasses both proteolytic and nonproteolytic functions. Examples of the latter type include evidence that monoubiquitylation of some transcriptional activators stimulates their activity. In addition, the proteasomal ATPases are recruited to many active promoters through binding to activators and play an important, nonproteolytic role in promoter escape and elongation. In this study, we report the discovery of a new nonproteolytic activity of the proteasome (specifically the proteasomal ATPases): the active destabilization of activator-promoter complexes. This reaction depends on the presence of an activation domain and ATP. Destabilization is inhibited in vitro and in vivo if the protein is monoubiquitylated or if ubiquitin is genetically fused to the activator. The fact that monoubiquitylated activator is resistant to the "stripping" activity of the proteasomal ATPases may explain, in part, why some activators require this modification in order to function efficiently.

MeSH Terms
Adenosine Triphosphatases/genetics,metabolism Adenosine Triphosphate/metabolism Blotting, Western Chromatin Immunoprecipitation DNA-Binding Proteins Gene Expression Regulation, Fungal HeLa Cells Humans Promoter Regions, Genetic/genetics Proteasome Endopeptidase Complex/metabolism Saccharomyces cerevisiae/genetics,growth & development,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism TATA Box/genetics Trans-Activators/metabolism Transcription Factors/genetics,metabolism Transcription, Genetic Transcriptional Activation Ubiquitin/metabolism
Chemicals
DNA-Binding Proteins GAL4 protein, S cerevisiae Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors Ubiquitin Adenosine Triphosphate Proteasome Endopeptidase Complex Adenosine Triphosphatases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ferdous Anwarul
Center for Biomedical Inventions and Department of Microbiology, University of Texas-Southwestern Medical Center, Dallas, Texas 75390, USA.
Sikder Devanjan
Gillette Thomas
Nalley Kip
Kodadek Thomas
Johnston Stephen Albert
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
2007-01-01
Epub
2006-00-13
Pages
112-23
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1759896
Subset
IM
Grants
NIGMS NIH HHS · R01 GM066380 · United States
NIGMS NIH HHS · GM066380 · United States
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