Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus.
The Hey protein family, comprising Hey1, Hey2 and HeyL in mammals, conveys Notch signals in many cell types. The helix-loop-helix (HLH) domain as well as the Orange domain, mediate homo- and heterodimerization of these transcription factors. Although distinct interaction partners have been identifie...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4466309?pdf=render |
id |
doaj-777af2af8d28402880b6aa4ec3715059 |
---|---|
record_format |
Article |
spelling |
doaj-777af2af8d28402880b6aa4ec37150592020-11-25T02:43:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e013028810.1371/journal.pone.0130288Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus.Daniela SalatAnja WinklerHenning UrlaubManfred GesslerThe Hey protein family, comprising Hey1, Hey2 and HeyL in mammals, conveys Notch signals in many cell types. The helix-loop-helix (HLH) domain as well as the Orange domain, mediate homo- and heterodimerization of these transcription factors. Although distinct interaction partners have been identified so far, their physiological relevance for Hey functions is still largely unclear. Using a tandem affinity purification approach and mass spectrometry analysis we identified members of an ubiquitin E3-ligase complex consisting of FBXO45, PAM and SKP1 as novel Hey1 associated proteins. There is a direct interaction between Hey1 and FBXO45, whereas FBXO45 is needed to mediate indirect Hey1 binding to SKP1. Expression of Hey1 induces translocation of FBXO45 and PAM into the nucleus. Hey1 is a short-lived protein that is degraded by the proteasome, but there is no evidence for FBXO45-dependent ubiquitination of Hey1. On the contrary, Hey1 mediated nuclear translocation of FBXO45 and its associated ubiquitin ligase complex may extend its spectrum to additional nuclear targets triggering their ubiquitination. This suggests a novel mechanism of action for Hey bHLH factors.http://europepmc.org/articles/PMC4466309?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniela Salat Anja Winkler Henning Urlaub Manfred Gessler |
spellingShingle |
Daniela Salat Anja Winkler Henning Urlaub Manfred Gessler Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus. PLoS ONE |
author_facet |
Daniela Salat Anja Winkler Henning Urlaub Manfred Gessler |
author_sort |
Daniela Salat |
title |
Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus. |
title_short |
Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus. |
title_full |
Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus. |
title_fullStr |
Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus. |
title_full_unstemmed |
Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus. |
title_sort |
hey bhlh proteins interact with a fbxo45 containing scf ubiquitin ligase complex and induce its translocation into the nucleus. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
The Hey protein family, comprising Hey1, Hey2 and HeyL in mammals, conveys Notch signals in many cell types. The helix-loop-helix (HLH) domain as well as the Orange domain, mediate homo- and heterodimerization of these transcription factors. Although distinct interaction partners have been identified so far, their physiological relevance for Hey functions is still largely unclear. Using a tandem affinity purification approach and mass spectrometry analysis we identified members of an ubiquitin E3-ligase complex consisting of FBXO45, PAM and SKP1 as novel Hey1 associated proteins. There is a direct interaction between Hey1 and FBXO45, whereas FBXO45 is needed to mediate indirect Hey1 binding to SKP1. Expression of Hey1 induces translocation of FBXO45 and PAM into the nucleus. Hey1 is a short-lived protein that is degraded by the proteasome, but there is no evidence for FBXO45-dependent ubiquitination of Hey1. On the contrary, Hey1 mediated nuclear translocation of FBXO45 and its associated ubiquitin ligase complex may extend its spectrum to additional nuclear targets triggering their ubiquitination. This suggests a novel mechanism of action for Hey bHLH factors. |
url |
http://europepmc.org/articles/PMC4466309?pdf=render |
work_keys_str_mv |
AT danielasalat heybhlhproteinsinteractwithafbxo45containingscfubiquitinligasecomplexandinduceitstranslocationintothenucleus AT anjawinkler heybhlhproteinsinteractwithafbxo45containingscfubiquitinligasecomplexandinduceitstranslocationintothenucleus AT henningurlaub heybhlhproteinsinteractwithafbxo45containingscfubiquitinligasecomplexandinduceitstranslocationintothenucleus AT manfredgessler heybhlhproteinsinteractwithafbxo45containingscfubiquitinligasecomplexandinduceitstranslocationintothenucleus |
_version_ |
1724771298651930624 |