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RHO methylation matters: a role for isoprenylcysteine carboxylmethyltransferase in cell migration and adhesion
- Source :
- Cell adhesionmigration. 5(1)
- Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- rac1 GTP-Binding Protein
rho GTP-Binding Proteins
RHOA
Cell
Protein Prenylation
RAC1
Plasma protein binding
Biology
Methylation
Cellular and Molecular Neuroscience
Prenylation
Cell Movement
Cell Line, Tumor
medicine
Cell Adhesion
Humans
rho-Specific Guanine Nucleotide Dissociation Inhibitors
Protein Methyltransferases
Cell adhesion
Guanine Nucleotide Dissociation Inhibitors
Commentary & View
Cell migration
Cell Biology
Cell biology
medicine.anatomical_structure
biology.protein
rhoA GTP-Binding Protein
Protein Processing, Post-Translational
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 19336926
- Volume :
- 5
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell adhesionmigration
- Accession number :
- edsair.doi.dedup.....476c0aa26897d0113ae0b9b112c4b645