Affordable Access

deepdyve-link
Publisher Website

A role for Rac3 GTPase in the regulation of autophagy.

Authors
  • Zhu, Wan Long
  • Hossain, Mohammed S
  • Guo, Dian Yan
  • Liu, Sen
  • Tong, Honglian
  • Khakpoor, Atefeh
  • Casey, Patrick J
  • Wang, Mei
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Oct 06, 2011
Volume
286
Issue
40
Pages
35291–35298
Identifiers
DOI: 10.1074/jbc.M111.280990
PMID: 21852230
Source
Medline
License
Unknown

Abstract

The process of autophagy is situated at the intersection of multiple cell signaling pathways, including cell metabolism, growth, and death, and hence is subject to multiple forms of regulation. We previously reported that inhibition of isoprenylcysteine carboxylmethyltransferase (Icmt), which catalyzes the final step in the post-translational prenylation of so-called CAAX proteins, results in the induction of autophagy which enhances cell death in some cancer cells. In this study, using siRNA-mediated knockdown of a group of small GTPases that are predicted Icmt substrates, we identify Rac3 GTPase as a negative regulator of the process of autophagy. Knockdown of Rac3, but not the closely related isoforms Rac1 and Rac2, results in induction of autophagy. Ectopic expression of Rac3, significantly rescues cells from autophagy and cell death induced by Icmt inhibition, strengthening the notion of an isoform-specific autophagy regulatory function of Rac3. This role of Rac3 was observed in multiple cell lines with varying Rac subtype expression profiles, suggesting its broad involvement in the process. The identification of this less-studied Rac member as a novel regulator provides new insight into autophagy and opens opportunities in identifying additional regulatory inputs of the process.

Report this publication

Statistics

Seen <100 times