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 prot eolytic 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, belongi ng to distinct families of metalloproteinases. Northern blot analysis of po ly(A)(+) RNAs isolated from a wide variety of human tissues demonstrated th at both genes are expressed in all examined tissues, which suggests that th ese enzymes play housekeeping roles in normal processes. Fluorescence in si tu hybridization experiments showed that the human FACE-1 gene maps to 1p34 , whereas FACE-2 is located at 11q13, a region frequently amplified in huma n 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 process es, including Ras proteins. (C) 1999 Academic Press.