| RHO methylation matters: a role for isoprenylcysteine carboxylmethyltransferase in cell migration and adhesion. | |
| | |
MedLine Citation:
|
PMID: 20798596 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Numerous proteins involved in diverse aspects of cell biology undergo a process of post-translational modification termed prenylation. The prenylation pathway consists of three enzymatic steps, the final of which is methylation of the carboxyl-terminal prenylcysteine formed in the first two steps by the enzyme isoprenylcysteine carboxylmethyltransferase (Icmt). Due to the prevalence of prenylated proteins in cancer biology, and the findings that several of the proteins are involved in processes controlling cell migration and adhesion, we sought to examine the role of Icmt - mediated methylation on cell behavior associated with metastasis. We found that inhibition of methylation reduces migration of the highly metastatic MDA-MB-231 breast cancer cell line. In addition, cell adhesion and cell spreading were also impaired by Icmt inhibition. Further investigation revealed that inhibition of Icmt significantly decreased the activation of both RhoA and Rac1, which are both prenylated proteins. The data obtained were consistent with the decreased activation being due to an increase in Rho GDP-dissociation inhibitor (GDI) binding by both proteins in the absence of their methylation. Importantly, the addition of exogenous RhoA or Rac1 to cells in which Icmt was inhibited was able to partially, but selectively, rescue directed and random migration, respectively. These results establish a role for Icmt-mediated methylation in cell migration, and point to specific prenylated proteins involved in this biology. The prenylation pathway has been targeted for oncogenic therapies, but the role of methylation in cell motility had been largely unexplored until now. The finding that methylation of Rho family members impacts on a specific component of their function provides an additional avenue through which to interrogate the biology of this important class of regulatory proteins. |
| | |
Authors:
|
Ian Cushman; Patrick J Casey |
Related Documents
:
|
17307336 - Sphingosine-1-phosphate initiates rapid retraction of pseudopodia by localized rhoa act... 9858476 - Cytoskeletal changes induced by graf, the gtpase regulator associated with focal adhesi... 8943416 - Rho is a negative regulator of human monocyte spreading. 18395046 - Mechanical homeostasis is altered in uterine leiomyoma. 21298436 - Regulation of vascular guanylyl cyclase by endothelial nitric oxide-dependent posttrans... 22545176 - Regulation of lysosomal secretion by cortactin drives fibronectin deposition and cell m... |
Publication Detail:
|
Type: Journal Article Date: 2011-01-01 |
Journal Detail:
|
Title: Cell adhesion & migration Volume: 5 ISSN: 1933-6926 ISO Abbreviation: Cell Adh Migr Publication Date: 2011 Jan-Feb |
Date Detail:
|
Created Date: 2011-01-28 Completed Date: 2011-04-18 Revised Date: 2012-01-02 |
Medline Journal Info:
|
Nlm Unique ID: 101469464 Medline TA: Cell Adh Migr Country: United States |
Other Details:
|
Languages: eng Pagination: 11-5 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Adhesion
/
physiology* Cell Line, Tumor / chemistry Cell Movement / physiology* Guanine Nucleotide Dissociation Inhibitors / chemistry* Humans Methylation Protein Binding Protein Methyltransferases / chemistry* Protein Prenylation / physiology Protein Processing, Post-Translational / physiology Signal Transduction / physiology rac1 GTP-Binding Protein / chemistry rho GTP-Binding Proteins / chemistry* rhoA GTP-Binding Protein / chemistry |
| Chemical | |
Reg. No./Substance:
|
0/Guanine Nucleotide Dissociation Inhibitors; 133312-85-3/rho guanine nucleotide dissociation inhibitors; EC 2.1.1.-/Protein Methyltransferases; EC 2.1.1.100/protein-S-isoprenylcysteine O-methyltransferase; EC 3.6.5.2/rac1 GTP-Binding Protein; EC 3.6.5.2/rho GTP-Binding Proteins; EC 3.6.5.2/rhoA GTP-Binding Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Time to taste: circadian clock function in the Drosophila gustatory system.
Next Document: Arabidopsis CPK3 plays extensive roles in various biological and environmental responses.