DNA-binding regulates site-specific ubiquitination of IRF-1.
Biochem J
; 449(3): 707-17, 2013 Feb 01.
Article
in En
| MEDLINE
| ID: mdl-23134341
ABSTRACT
Understanding the determinants for site-specific ubiquitination by E3 ligase components of the ubiquitin machinery is proving to be a challenge. In the present study we investigate the role of an E3 ligase docking site (Mf2 domain) in an intrinsically disordered domain of IRF-1 [IFN (interferon) regulatory factor-1], a short-lived IFNγ-regulated transcription factor, in ubiquitination of the protein. Ubiquitin modification of full-length IRF-1 by E3 ligases such as CHIP [C-terminus of the Hsc (heat-shock cognate) 70-interacting protein] and MDM2 (murine double minute 2), 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
Interferon Regulatory Factor-1
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Biochem J
Year:
2013
Document type:
Article
Affiliation country:
United kingdom