Rig is a novel Ras-related protein and potential neural tumor suppressor.
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.
Ellis
Chad A
CA
Department of Cell and Cancer Biology, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Suite 307, Rockville, MD 20850-3300, USA.
Vos
Michele D
MD
Howell
Heather
H
Vallecorsa
Teresa
T
Fults
Daniel W
DW
Clark
Geoffrey J
GJ
D016475:3T3 Cells; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002470:Cell Survival; D003001:Cloning, Molecular; D020224:Expressed Sequence Tags; D020558:GTP Phosphohydrolases; D015723:Gene Library; D016147:Genes, Tumor Suppressor; D006801:Humans; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D009423:Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D017368:Protein Prenylation; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D008156:Luciferases; C468772:DIRAS1 protein, human; D020558:GTP Phosphohydrolases