SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments.

LITAF is a small cellular protein with an unknown function. The C-terminus of LITAF contains a highly conserved domain termed the SIMPLE-like domain (SLD), while the N-terminus contains two PPXY motifs that mediate protein-protein interactions with WW-domain containing proteins. LITAF also harbors t...

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Main Authors: Heather E Eaton, Guillaume Desrochers, Samuel B Drory, Julie Metcalf, Annie Angers, Craig R Brunetti
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-02-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3033906?pdf=render
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author Heather E Eaton
Guillaume Desrochers
Samuel B Drory
Julie Metcalf
Annie Angers
Craig R Brunetti
author_facet Heather E Eaton
Guillaume Desrochers
Samuel B Drory
Julie Metcalf
Annie Angers
Craig R Brunetti
author_sort Heather E Eaton
collection DOAJ
description LITAF is a small cellular protein with an unknown function. The C-terminus of LITAF contains a highly conserved domain termed the SIMPLE-like domain (SLD), while the N-terminus contains two PPXY motifs that mediate protein-protein interactions with WW-domain containing proteins. LITAF also harbors two endosome/lysosome targeting sequences at its C-terminus, but there has been conflicting reports regarding its intracellular localization. Here, we demonstrate that LITAF is localized to the late endosome/lysosomal compartment in a variety of cell lines. We also show that Itch, a WW-domain containing protein, and LITAF strongly interact and that this interaction depends on the two PPXY motifs in the N-terminus of LITAF. Interestingly, co-expression of LITAF with Itch induces major changes in Itch intracellular localization, bringing Itch from the trans-Golgi network to lysosomes. We show that this re-localization is dependent upon the interaction with the PPXY sequences of LITAF, since disruption of these binding motifs completely abrogates Itch re-localization.
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spelling doaj.art-9cd2403a354341a78081352b86d30b842022-12-22T01:14:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-02-0162e1687310.1371/journal.pone.0016873SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments.Heather E EatonGuillaume DesrochersSamuel B DroryJulie MetcalfAnnie AngersCraig R BrunettiLITAF is a small cellular protein with an unknown function. The C-terminus of LITAF contains a highly conserved domain termed the SIMPLE-like domain (SLD), while the N-terminus contains two PPXY motifs that mediate protein-protein interactions with WW-domain containing proteins. LITAF also harbors two endosome/lysosome targeting sequences at its C-terminus, but there has been conflicting reports regarding its intracellular localization. Here, we demonstrate that LITAF is localized to the late endosome/lysosomal compartment in a variety of cell lines. We also show that Itch, a WW-domain containing protein, and LITAF strongly interact and that this interaction depends on the two PPXY motifs in the N-terminus of LITAF. Interestingly, co-expression of LITAF with Itch induces major changes in Itch intracellular localization, bringing Itch from the trans-Golgi network to lysosomes. We show that this re-localization is dependent upon the interaction with the PPXY sequences of LITAF, since disruption of these binding motifs completely abrogates Itch re-localization.http://europepmc.org/articles/PMC3033906?pdf=render
spellingShingle Heather E Eaton
Guillaume Desrochers
Samuel B Drory
Julie Metcalf
Annie Angers
Craig R Brunetti
SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments.
PLoS ONE
title SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments.
title_full SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments.
title_fullStr SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments.
title_full_unstemmed SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments.
title_short SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments.
title_sort simple litaf expression induces the translocation of the ubiquitin ligase itch towards the lysosomal compartments
url http://europepmc.org/articles/PMC3033906?pdf=render
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