Files and links (1)
Published, Version of Record (VoR)Open Access (License Unspecified), Open
Journal article
Adenovirus E4orf4 Hijacks Rho GTPase-dependent Actin Dynamics to Kill Cells: A Role for Endosome-associated Actin Assembly
Molecular biology of the cell, v 17(7), pp 3329-3344
Jul 2006
PMID: 16687574
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The adenovirus early region 4 ORF4 protein (E4orf4) triggers a novel death program that bypasses classical apoptotic pathways in human cancer cells. Deregulation of the cell cytoskeleton is a hallmark of E4orf4 killing that relies on Src family kinases and E4orf4 phosphorylation. However, the cytoskeletal targets of E4orf4 and their role in the death process are unknown. Here, we show that E4orf4 translocates to cytoplasmic sites and triggers the assembly of a peculiar juxtanuclear actin–myosin network that drives polarized blebbing and nuclear shrinkage. We found that E4orf4 activates the myosin II motor and triggers de novo actin polymerization in the perinuclear region, promoting endosomes recruitment to the sites of actin assembly. E4orf4-induced actin dynamics requires interaction with Src family kinases and involves a spatial regulation of the Rho GTPases pathways Cdc42/N-Wasp, RhoA/Rho kinase, and Rac1, which make distinct contributions. Remarkably, activation of the Rho GTPases is required for induction of apoptotic-like cell death. Furthermore, inhibition of actin dynamics per se dramatically impairs E4orf4 killing. This work provides strong support for a causal role for endosome-associated actin dynamics in E4orf4 killing and in the regulation of cancer cell fate.
Metrics
Details
- Title
- Adenovirus E4orf4 Hijacks Rho GTPase-dependent Actin Dynamics to Kill Cells: A Role for Endosome-associated Actin Assembly
- Creators
- Amélie Robert - Hôtel-Dieu de QuébecNicolas Smadja-Lamère - Hôtel-Dieu de QuébecMarie-Claude Landry - Hôtel-Dieu de QuébecClaudia Champagne - Hôtel-Dieu de QuébecRyan Petrie - McGill UniversityNathalie Lamarche-Vane - McGill UniversityHiroshi Hosoya - Hiroshima UniversityJosée N. Lavoie - Hôtel-Dieu de Québec
- Contributors
- J. Silvio Gutkind (Editor)
- Publication Details
- Molecular biology of the cell, v 17(7), pp 3329-3344
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000238721000040
- Scopus ID
- 2-s2.0-33745625096
- Other Identifier
- 991020100054704721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology