DNA-binding regulates site-specific ubiquitination of IRF-1

Vivien Landre, Emmanuelle Pion, Vikram Narayan, Dimitris P. Xirodimast, Kathryn L. Ball

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)707-717
Number of pages11
JournalBiochemical Journal
Issue number3
Publication statusPublished - Feb 2013

Keywords / Materials (for Non-textual outputs)

  • C-terminus of the heat-shock cognate 70-interacting protein (CHIP)
  • DNA binding
  • interferon regulatory factor 1 (IRF-1)
  • murine double minute 2 (MDM2)
  • transcription
  • ubiquitination


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