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A role for Rac3 GTPase in the regulation of autophagy.

Publication ,  Journal Article
Zhu, WL; Hossain, MS; Guo, DY; Liu, S; Tong, H; Khakpoor, A; Casey, PJ; Wang, M
Published in: J Biol Chem
October 7, 2011

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.

Duke Scholars

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

October 7, 2011

Volume

286

Issue

40

Start / End Page

35291 / 35298

Location

United States

Related Subject Headings

  • rac GTP-Binding Proteins
  • Signal Transduction
  • RNA, Small Interfering
  • Protein Processing, Post-Translational
  • Protein Isoforms
  • Microscopy, Fluorescence
  • Humans
  • Hela Cells
  • HeLa Cells
  • GTP-Binding Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhu, W. L., Hossain, M. S., Guo, D. Y., Liu, S., Tong, H., Khakpoor, A., … Wang, M. (2011). A role for Rac3 GTPase in the regulation of autophagy. J Biol Chem, 286(40), 35291–35298. https://doi.org/10.1074/jbc.M111.280990
Zhu, Wan Long, Mohammed S. Hossain, Dian Yan Guo, Sen Liu, Honglian Tong, Atefeh Khakpoor, Patrick J. Casey, and Mei Wang. “A role for Rac3 GTPase in the regulation of autophagy.J Biol Chem 286, no. 40 (October 7, 2011): 35291–98. https://doi.org/10.1074/jbc.M111.280990.
Zhu WL, Hossain MS, Guo DY, Liu S, Tong H, Khakpoor A, et al. A role for Rac3 GTPase in the regulation of autophagy. J Biol Chem. 2011 Oct 7;286(40):35291–8.
Zhu, Wan Long, et al. “A role for Rac3 GTPase in the regulation of autophagy.J Biol Chem, vol. 286, no. 40, Oct. 2011, pp. 35291–98. Pubmed, doi:10.1074/jbc.M111.280990.
Zhu WL, Hossain MS, Guo DY, Liu S, Tong H, Khakpoor A, Casey PJ, Wang M. A role for Rac3 GTPase in the regulation of autophagy. J Biol Chem. 2011 Oct 7;286(40):35291–35298.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

October 7, 2011

Volume

286

Issue

40

Start / End Page

35291 / 35298

Location

United States

Related Subject Headings

  • rac GTP-Binding Proteins
  • Signal Transduction
  • RNA, Small Interfering
  • Protein Processing, Post-Translational
  • Protein Isoforms
  • Microscopy, Fluorescence
  • Humans
  • Hela Cells
  • HeLa Cells
  • GTP-Binding Proteins