A role for Rac3 GTPase in the regulation of autophagy.
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.
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- 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
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
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