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PMID: 10454536 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Suppression of Ras-induced apoptosis by the Rac GTPase.

Molecular and cellular biology ·Vol. 19 ·No. 9 ·1999-09-00 ·Pages 5892-901

Joneson T, Bar-Sagi D

Abstract

Ras is an essential component of signal transduction pathways that control cell proliferation, differentiation, and survival. In this study we have examined the cellular responses to high-intensity Ras signaling. Expression of increasing amounts of the oncogenic form of human HRas, HRasV12, results in a dose-dependent induction of apoptosis in both primary and immortalized cells. The induction of apoptosis by HRasV12 is blocked by activated Rac and potentiated by dominant interfering Rac. The ability of Rac to suppress Ras-induced apoptosis is dependent on effector pathway(s) controlled by the insert region and is linked to the activation of NF-kappaB. The apoptotic effect of HRasV12 requires the activation of both the ERK and JNK mitogen-activated protein kinase cascade and is independent of p53. These results demonstrate a role for Rac in controlling signals that are necessary for cell survival, and suggest a mechanism by which Rac activity can confer growth advantage to cells transformed by the ras oncogene.

MeSH Terms
Animals Apoptosis/physiology Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Cycle Proteins/metabolism Cell Line Cell Survival/physiology GTP-Binding Proteins/metabolism GTPase-Activating Proteins Gene Expression Growth Substances/physiology Humans Mice NF-kappa B/metabolism Plasmids/genetics Proteins/genetics,physiology Rats Signal Transduction Tumor Suppressor Protein p53/metabolism cdc42 GTP-Binding Protein ras GTPase-Activating Proteins ras Proteins/genetics,physiology
Chemicals
Cell Cycle Proteins GTPase-Activating Proteins Growth Substances NF-kappa B Proteins Tumor Suppressor Protein p53 ras GTPase-Activating Proteins Calcium-Calmodulin-Dependent Protein Kinases GTP-Binding Proteins cdc42 GTP-Binding Protein ras Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Joneson T
Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, New York 11794-5222, USA.
Bar-Sagi D
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.9.5892
Published
1999-09-00
Pages
5892-901
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84438
Subset
IM
Grants
NCI NIH HHS · R01 CA055360 · United States
NCI NIH HHS · R37 CA055360 · United States
NCI NIH HHS · R56 CA055360 · United States
NCI NIH HHS · CA55360 · United States
External Links
PubMed source DOI: 10.1128/MCB.19.9.5892 PMC Full Text View journal details
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