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PNAS 99 (15): 9876-9881

Copyright © 2002 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / CELL BIOLOGY

Rig is a novel Ras-related protein and potential neural tumor suppressor

Chad A. Ellis*, Michele D. Vos*, Heather Howell*, Teresa Vallecorsa*, Daniel W. Fults{dagger}, and Geoffrey J. Clark*,{ddagger}

*Department of Cell and Cancer Biology, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Suite 307, Rockville, MD 20850-3300; and {dagger}Department of Neurosurgery, University of Utah School of Medicine and Huntsman Cancer Institute, Salt Lake City, UT 84132

Received for publication April 2, 2002.

Abstract: The Ras superfamily consists of a large group of monomeric GTPases demonstrating homology to Ras oncoproteins. Although structurally similar, Ras-superfamily proteins are functionally diverse. Whereas some members exhibit oncogenic properties, others may serve as tumor suppressors. We have identified a novel Ras-related protein that suppresses cell growth and have designated it Rig (Ras-related inhibitor of cell growth). Overexpression of Rig inhibited Ras-mediated cellular transformation and activation of downstream signaling in NIH 3T3 cells. rig mRNA is expressed at high levels in normal cardiac and neural tissue. However, Rig protein expression is frequently lost or down-regulated in neural tumor-derived cell lines and primary human neural tumors. Moreover, expression of exogenous Rig in human astrocytoma cells suppressed growth. Rig has a C-terminal CAAX motif that codes for posttranslational modification by both farnesyl and geranylgeranyl isoprenoid lipids. Consequently, Rig may play a role in the cellular response to farnesyl transferase inhibitors. Rig bears 63% overall sequence homology to a recently described Ras-family member Noey2, a tumor suppressor in breast and ovarian tissue. Therefore, Rig and Noey2 may represent a new subfamily of Ras-like tumor suppressors.

{ddagger} To whom reprint requests should be addressed. E-mail: clarkg{at}pop.nci.nih.gov.

Edited by Michael H. Wigler, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, and approved May 15, 2002

This paper was submitted directly (Track II) to the PNAS office.

Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AY056037).

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