RASL11A, member of a novel small monomeric GTPase gene family, is down-regulated in prostate tumors.
We performed a genome-wide search for novel loci encoding for Ras-related proteins based on the genome mapping coordinates of the cancer-derived EST dataset at GenBank. Partial sequences from two novel human genes were identified and subsequently used for full length transcript cloning. RASL11A and ARL9 belong to two novel subfamilies coding for small GTPases that we found to be highly conserved among eukaryotes. The Arl9/Arl10 subfamily displays a conserved interswitch toggle that places it evolutionarily closer to the Arf family. Rasl11 proteins are more closely related to the Ras branch of GTPases. All orthologues newly identified here exhibit an Asn residue in place of the highly conserved Thr35 of the G domain, suggesting that the universal switch mechanism of small GTPases may be structurally different in this subfamily. We determined by Northern blot that RASL11A is transcribed in several human tissues and that it is down-regulated in prostate tumors as measured by quantitative real-time PCR. These results highlight a previously uncharacterized subfamily of Ras-related genes that may have a tumor suppressor role in prostate cancer.
Louro
Rodrigo
R
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil.
Nakaya
Helder I
HI
Paquola
Apuã C M
AC
Martins
Elizabeth A L
EA
da Silva
Aline M
AM
Verjovski-Almeida
Sergio
S
Reis
Eduardo M
EM
D020727:ADP-Ribosylation Factors / Q000096:biosynthesis* / Q000235:genetics*; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D017124:Conserved Sequence; D015536:Down-Regulation; D020224:Expressed Sequence Tags; D005260:Female; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010802:Phylogeny; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D012333:RNA, Messenger; D020558:GTP Phosphohydrolases; C484949:RASL11A protein, human; D020727:ADP-Ribosylation Factors; C484950:ARL9 protein, human; D020559:Monomeric GTP-Binding Proteins