TY  - JOUR
A1  - Murali, Arun
A1  - Shin, Jaeyoung
A1  - Yurugi, Hajime
A1  - Krishnan, Aswini
A1  - Akutsu, Masato
A1  - Carpy, Alejandro
A1  - Maček, Boris
A1  - Rajalingam, Krishnaraj
T1  - Ubiquitin-dependent regulation of Cdc42 by XIAP
T2  - Cell death & disease
N2  - Rho GTPases control fundamental cellular processes and Cdc42 is a well-studied member of the family that controls filopodia formation and cell migration. Although the regulation of Cdc42 activity by nucleotide binding is well documented, the mechanisms driving its proteostasis are not clear. Here, we demonstrate that the highly conserved, RING domain containing E3 ubiquitin ligase XIAP controls the protein stability of Cdc42. XIAP binds to Cdc42 and directly conjugates poly ubiquitin chains to the Lysine 166 of Cdc42 targeting it for proteasomal degradation. Depletion of XIAP led to an increased protein stability and activity of Cdc42 in normal and tumor cells. Consistently, loss of XIAP enhances filopodia formation in a Cdc42-dependent manner and this phenomenon phenocopies EGF stimulation. Further, XIAP depletion promotes lung colonization of tumor cells in mice in a Cdc42-dependent manner. These observations shed molecular insights into ubiquitin-dependent regulation of Cdc42 and that of actin cytoskeleton.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46311
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-463119
SN  - 2041-4889
N1  - Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
VL  - 8
IS  - 6, e2900
SP  - 1
EP  - 10
PB  - Nature Publishing Group
CY  - London [u. a.]
ER  -