Document Detail

DNA-binding regulates site-specific ubiquitination of IRF-1.
MedLine Citation:
PMID:  23134341     Owner:  NLM     Status:  Publisher    
Understanding the determinants for site-specific ubiquitination by E3-ligase components of the ubiquitin-machinery is proving to be a challenge. Here we investigate the role of an E3-ligase docking site (Mf2-domain) in an intrinsically disordered domain of IRF-1, a short-lived IFN-γ regulated transcription factor, in ubiquitination of the protein. Ubiquitin modification of full-length IRF-1 by E3-ligases like CHIP and MDM2, which dock to the Mf2-domain was specific for lysine residues found predominantly in loop structures that extend from the DNA-binding domain, whereas no modification was detected in the more conformationally flexible C-terminal half of the protein. The E3-docking site was not available when IRF-1 was in its DNA bound conformation and cognate DNA-binding sequences strongly suppressed ubiquitination highlighting a strict relationship between ligase binding and site-specific modification at residues in the DNA-binding domain. Hyperubiquitination of a non-DNA binding mutant supports a mechanism where an active DNA-bound pool of IRF-1 is protected from polyubiquitination and degradation.
Vivien Landré; Emmanuelle Pion; Vikram Narayan; Dimitris P Xirodimas; Kathryn L Ball
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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