PUBLICATION

Molecular Analysis of the HOXA2-Dependent Degradation of RCHY1

Authors
Bridoux, L., Deneyer, N., Bergiers, I., Rezsohazy, R.
ID
ZDB-PUB-240502-27
Date
2015
Source
PLoS One   10: e0141347e0141347 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Mice
  • Enzyme Stability
  • Homeodomain Proteins/chemistry
  • Homeodomain Proteins/physiology*
  • Proteasome Endopeptidase Complex/metabolism
  • Proteolysis
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Gene Expression
  • Animals
  • Ubiquitin-Protein Ligases/metabolism*
  • HEK293 Cells
  • Humans
  • Cell Nucleus/enzymology
  • Half-Life
  • Embryonic Development
  • Gene Expression Regulation, Developmental
PubMed
26496426 Full text @ PLoS One
Abstract
The homeodomain transcription factor Hoxa2 interacts with the RING-finger type E3 ubiquitin ligase RCHY1 and induces its proteasomal degradation. In this work, we dissected this non-transcriptional activity of Hoxa2 at the molecular level. The Hoxa2-mediated decay of RCHY1 involves both the 19S and 20S proteasome complexes. It relies on both the Hoxa2 homeodomain and C-terminal moiety although no single deletion in the Hoxa2 sequence could disrupt the RCHY1 interaction. That the Hoxa2 homeodomain alone could mediate RCHY1 binding is consistent with the shared ability all the Hox proteins we tested to interact with RCHY1. Nonetheless, the ability to induce RCHY1 degradation although critically relying on the homeodomain is not common to all Hox proteins. This identifies the homeodomain as necessary but not sufficient for what appears to be an almost generic Hox protein activity. Finally we provide evidence that the Hoxa2-induced degradation of RCHY1 is evolutionarily conserved among vertebrates. These data therefore support the hypothesis that the molecular and functional interaction between Hox proteins and RCHY1 is an ancestral Hox property.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping