RRP22 is a farnesylated, nucleolar, Ras-related protein with tumor suppressor potential.
Ras proteins are members of a superfamily of related small GTPases. Some members, such as Ras, are oncogenic. However, other members seem to serve as tumor suppressors, such as Rig and Noey2. We now identify and characterize a novel member of the Ras superfamily, RRP22. Like Ras, RRP22 can be posttranslationally modified by farnesyl. Unlike Ras, RRP22 inhibits cell growth and promotes caspase-independent cell death. Examination of human tumor cells shows that RRP22 is frequently down-regulated due to promoter methylation. Moreover, reexpression of RRP22 in an RRP22-negative neural tumor cell line impairs its growth in soft agar. Unusually for a Ras-related protein, RRP22 localizes to the nucleolus in a GTP-dependent manner, suggesting a novel mechanism of action. Thus, we identify a new member of the Ras superfamily that can serve as a potential tumor suppressor.
Elam
Candice
C
Department of Cell and Cancer Biology, National Cancer Institute, 9610 Medical Center Drive, Rockville, MD 20820, USA.
Hesson
Luke
L
Vos
Michele D
MD
Eckfeld
Kristin
K
Ellis
Chad A
CA
Bell
Aaron
A
Krex
Dietmar
D
Birrer
Michael J
MJ
Latif
Farida
F
Clark
Geoffrey J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D017124:Conserved Sequence; D019175:DNA Methylation; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D017368:Protein Prenylation; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C104142:RASL10A protein, human; D018631:ras Proteins