The homeodomain transcription factor Hoxa2 interacts with and promotes the proteasomal degradation of the E3 ubiquitin protein ligase RCHY1.

Hox proteins are conserved homeodomain transcription factors known to be crucial regulators of animal development. As transcription factors, the functions and modes of action (co-factors, target genes) of Hox proteins have been very well studied in a multitude of animal models. However, a handful of...

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Main Authors: Isabelle Bergiers, Laure Bridoux, Nathan Nguyen, Jean-Claude Twizere, René Rezsöhazy
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3820564?pdf=render
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author Isabelle Bergiers
Laure Bridoux
Nathan Nguyen
Jean-Claude Twizere
René Rezsöhazy
author_facet Isabelle Bergiers
Laure Bridoux
Nathan Nguyen
Jean-Claude Twizere
René Rezsöhazy
author_sort Isabelle Bergiers
collection DOAJ
description Hox proteins are conserved homeodomain transcription factors known to be crucial regulators of animal development. As transcription factors, the functions and modes of action (co-factors, target genes) of Hox proteins have been very well studied in a multitude of animal models. However, a handful of reports established that Hox proteins may display molecular activities distinct from gene transcription regulation. Here, we reveal that Hoxa2 interacts with 20S proteasome subunits and RCHY1 (also known as PIRH2), an E3 ubiquitin ligase that targets p53 for degradation. We further show that Hoxa2 promotes proteasome-dependent degradation of RCHY1 in an ubiquitin-independent manner. Correlatively, Hoxa2 alters the RCHY1-mediated ubiquitination of p53 and promotes p53 stabilization. Together, our data establish that Hoxa2 can regulate the proteasomal degradation of RCHY1 and stabilization of p53.
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spelling doaj.art-0e3a1c9caf2e4fa7a2cc77cbccf139512022-12-22T03:46:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8038710.1371/journal.pone.0080387The homeodomain transcription factor Hoxa2 interacts with and promotes the proteasomal degradation of the E3 ubiquitin protein ligase RCHY1.Isabelle BergiersLaure BridouxNathan NguyenJean-Claude TwizereRené RezsöhazyHox proteins are conserved homeodomain transcription factors known to be crucial regulators of animal development. As transcription factors, the functions and modes of action (co-factors, target genes) of Hox proteins have been very well studied in a multitude of animal models. However, a handful of reports established that Hox proteins may display molecular activities distinct from gene transcription regulation. Here, we reveal that Hoxa2 interacts with 20S proteasome subunits and RCHY1 (also known as PIRH2), an E3 ubiquitin ligase that targets p53 for degradation. We further show that Hoxa2 promotes proteasome-dependent degradation of RCHY1 in an ubiquitin-independent manner. Correlatively, Hoxa2 alters the RCHY1-mediated ubiquitination of p53 and promotes p53 stabilization. Together, our data establish that Hoxa2 can regulate the proteasomal degradation of RCHY1 and stabilization of p53.http://europepmc.org/articles/PMC3820564?pdf=render
spellingShingle Isabelle Bergiers
Laure Bridoux
Nathan Nguyen
Jean-Claude Twizere
René Rezsöhazy
The homeodomain transcription factor Hoxa2 interacts with and promotes the proteasomal degradation of the E3 ubiquitin protein ligase RCHY1.
PLoS ONE
title The homeodomain transcription factor Hoxa2 interacts with and promotes the proteasomal degradation of the E3 ubiquitin protein ligase RCHY1.
title_full The homeodomain transcription factor Hoxa2 interacts with and promotes the proteasomal degradation of the E3 ubiquitin protein ligase RCHY1.
title_fullStr The homeodomain transcription factor Hoxa2 interacts with and promotes the proteasomal degradation of the E3 ubiquitin protein ligase RCHY1.
title_full_unstemmed The homeodomain transcription factor Hoxa2 interacts with and promotes the proteasomal degradation of the E3 ubiquitin protein ligase RCHY1.
title_short The homeodomain transcription factor Hoxa2 interacts with and promotes the proteasomal degradation of the E3 ubiquitin protein ligase RCHY1.
title_sort homeodomain transcription factor hoxa2 interacts with and promotes the proteasomal degradation of the e3 ubiquitin protein ligase rchy1
url http://europepmc.org/articles/PMC3820564?pdf=render
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