Regulation of Transcriptional Activators by DNA-Binding Domain Ubiquitination

Vivien Landré, Bhindu Revi, Maria Gil Mir, Chandra Verma, Ted R Hupp, Nick Gilbert, Kathryn L Ball

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Ubiquitin is a key component of the regulatory network that maintains gene expression in eukaryotes, yet the molecular mechanism(s) by which non-degradative ubiquitination modulates transcriptional activator (TA) function is unknown. Here endogenous p53, a stress-activated transcription factor required to maintain health, is stably monoubiquitinated, following pathway activation by IR or Nutlin-3 and localized to the nucleus where it becomes tightly associated with chromatin. Comparative structure–function analysis and in silico modelling demonstrate a direct role for DNA-binding domain (DBD) monoubiquitination in TA activation. When attached to the DBD of either p53, or a second TA IRF-1, ubiquitin is orientated towards, and makes contact with, the DNA. The contact is made between a predominantly cationic surface on ubiquitin and the anionic DNA. Our data demonstrate an unexpected role for ubiquitin in the mechanism of TA-activity enhancement and provides insight into a new level of transcriptional regulation.
Original languageEnglish
Pages (from-to)903–916
JournalCell Death & Differentiation (CDD)
Issue number5
Early online date31 Mar 2017
Publication statusPublished - May 2017

Keywords / Materials (for Non-textual outputs)

  • p53
  • ubiquitination
  • post‐translational modification
  • transcription
  • MDM2


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