IAPs as E3 ligases of Rac1 : shaping the move

Inhibitors of Apoptosis Proteins (IAPs) are well-studied E3 ubiquitin ligases predominantly known for regulation of apoptosis. We uncovered that IAPs can function as a direct E3 ubiquitin ligase of RhoGTPase Rac1. cIAP1 
Inhibitors of Apoptosis Proteins (IAPs) are well-studied E3 ubiquitin ligases predominantly known for regulation of apoptosis. We uncovered that IAPs can function as a direct E3 ubiquitin ligase of RhoGTPase Rac1. cIAP1 and XIAP directly conjugate polyubiquitin chains to Lysine 147 of activated Rac1 and target it for proteasomal degradation. Consistently, loss of these IAPs by various strategies led to stabilization of Rac1 and mesenchymal mode of migration in tumor cells. IAPs also regulate Rac1 degradation upon RhoGDI1 depletion and CNF1 toxin treatment. Our observations revealed an evolutionarily conserved role of IAPs in regulating Rac1 stability shedding light on to the mechanisms behind ubiquitination–dependent inactivation of Rac1 signaling.
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Metadaten
Author:Tripat Kaur Oberoi-Khanuja, Krishnaraj Rajalingam
URN:urn:nbn:de:hebis:30:3-289354
DOI:http://dx.doi.org/10.4161/sgtp.19988
ISSN:2154-1256
ISSN:2154-1248
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=22790203
Parent Title (English):Small GTPases
Publisher:Landes Bioscience
Place of publication:Austin, Tex.
Document Type:Article
Language:English
Date of Publication (online):2012/04/01
Date of first Publication:2012/04/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/02/21
Tag:E3 ligase; IAPs; Proteasome; Rac1; RhoA; RhoGTPases; Ubiquitination; XIAP; amoeboid; cIAP1; cell migration; mesenchymal; plasticity; ubiquitin
Volume:3
Issue:2
Pagenumber:6
First Page:131
Last Page:136
Note:
Copyright © 2012 Landes Bioscience. This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
HeBIS PPN:332403041
Institutes:Biochemie und Chemie
Medizin
Dewey Decimal Classification:570 Biowissenschaften; Biologie
610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0

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