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 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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Author:Tripat Kaur Oberoi-Khanuja, Krishnaraj RajalingamORCiDGND
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/22790203
Parent Title (English):Small GTPases
Publisher:Landes Bioscience
Place of publication:Austin, Tex.
Document Type:Article
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
Page Number:6
First Page:131
Last Page:136
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.
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Medizin / Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell 3.0