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PMID: 12193475 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

RhoA biological activity is dependent on prenylation but independent of specific isoprenoid modification.

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research ·Vol. 13 ·No. 8 ·2002-08-00 ·Pages 363-73

Solski PA, Helms W, Keely PJ, Su L, Der CJ

Abstract

Recent studies showed that specific isoprenoid modification may be critical for RhoB subcellular location and function. Therefore, we determined whether the function of the highly related RhoA protein is also critically dependent on specific isoprenoid modification: (a) in contrast to observations with RhoB or Ras proteins, where farnesylated and geranylgeranylated versions showed differences in subcellular location, both prenylated versions of RhoA showed the same plasma membrane and cytosolic location; (b) a farnesylated version of activated RhoA(63L) retained the same diverse functions as the normally geranylgeranylated RhoA(63L) protein, and both proteins show indistinguishable abilities to stimulate gene expression, cause growth transformation of NIH 3T3 mouse fibroblasts, to stimulate the motility of T47D human breast epithelial cells, and to block HIV-1 viral replication and gene expression; and (c) cells expressing farnesylated RhoA retained sensitivity to the growth inhibition caused by inhibition of geranylgeranyltransferase I, indicating that other proteins are critical targets for inhibitors of geranylgeranylation.

MeSH Terms
3T3 Cells Alkyl and Aryl Transferases/metabolism Animals Cell Division/physiology Cell Movement/physiology Cyclin D1/genetics Eukaryotic Cells/metabolism Farnesyltranstransferase HIV-1/growth & development Mice Mutagenesis/physiology NF-kappa B/genetics Polyisoprenyl Phosphates/metabolism Promoter Regions, Genetic/physiology Protein Prenylation Serum Response Factor/genetics Transcriptional Activation/physiology Virus Replication/physiology rhoA GTP-Binding Protein/genetics,metabolism rhoB GTP-Binding Protein/metabolism
Chemicals
NF-kappa B Polyisoprenyl Phosphates Serum Response Factor Cyclin D1 Alkyl and Aryl Transferases geranylgeranyltransferase type-I Farnesyltranstransferase rhoA GTP-Binding Protein rhoB GTP-Binding Protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Solski Patricia A
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Departments of Pharmacology, Chapel Hill, North Carolina 27599, USA.
Helms Whitney
Keely Patricia J
Su Lishan
Der Channing J
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Article Info
Journal
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
Abbr.
Cell Growth Differ
ISSN
1044-9523
Published
2002-08-00
Pages
363-73
Language
English
Region
United States
NLM ID
9100024
PMCID
PMC4415366
Subset
IM
Grants
NCI NIH HHS · R01 CA042978 · United States
NIAID NIH HHS · AI48407 · United States
NIAID NIH HHS · R56 AI048407 · United States
NCI NIH HHS · CA63071 · United States
NCI NIH HHS · CA55008 · United States
NCI NIH HHS · CA42978 · United States
NIAID NIH HHS · R01 AI048407 · United States
NCI NIH HHS · R01 CA063071 · United States
External Links
PubMed source PMC Full Text
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