Identification and chromosomal location of two human genes encoding enzymes potentially involved in proteolytic maturation of farnesylated proteins.
Two human cDNAs encoding proteins similar to yeast enzymes involved in proteolytic processing of farnesylated proteins like a-factor mating pheromone and Ras2p have been cloned from an ovary cDNA library. These proteins have been tentatively called Face-1 and Face-2 (farnesylated protein-converting enzymes 1 and 2), respectively, and are integral membrane proteins, belonging to distinct families of metalloproteinases. Northern blot analysis of poly(A)+ RNAs isolated from a wide variety of human tissues demonstrated that both genes are expressed in all examined tissues, which suggests that these enzymes play housekeeping roles in normal processes. Fluorescence in situ hybridization experiments showed that the human FACE-1 gene maps to 1p34, whereas FACE-2 is located at 11q13, a region frequently amplified in human carcinomas and lymphomas. On the basis of these results, we suggest that inhibition of Face-1 and/or Face-2 could be part of strategies directed to block the functioning of prenylated proteins activated in oncogenic processes, including Ras proteins.
Freije
J M
JM
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, Oviedo, 33006-, Spain.
Blay
P
P
Pendás
A M
AM
Cadiñanos
J
J
Crespo
P
P
López-Otín
C
C
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D010450:Endopeptidases; D005260:Female; D015870:Gene Expression; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D008074:Lipoproteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D045726:Metalloproteases; D008969:Molecular Sequence Data; D043484:Proprotein Convertases; D011498:Protein Precursors / Q000378:metabolism*; D017368:Protein Prenylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic; D018631:ras Proteins / Q000378:metabolism
D018076:DNA, Complementary; D008074:Lipoproteins; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D010450:Endopeptidases; D045726:Metalloproteases; D043484:Proprotein Convertases; C491326:RCE1 protein, human; C105193:RCE1 protein, S cerevisiae; D008666:Metalloendopeptidases; C120130:ZMPSTE24 protein, human; D018631:ras Proteins