Elsevier

Genomics

Volume 58, Issue 3, 15 June 1999, Pages 270-280
Genomics

Regular Article
Identification and Chromosomal Location of Two Human Genes Encoding Enzymes Potentially Involved in Proteolytic Maturation of Farnesylated Proteins

https://doi.org/10.1006/geno.1999.5834Get rights and content

Abstract

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.

References (35)

  • R.E. Barrington et al.

    A farnesyltransferase inhibitor induces tumor regression in transgenic mice harboring multiple oncogenic mutations by mediating alterations in both cell cycle control and apoptosis

    Mol. Cell. Biol.

    (1998)
  • J.L. Bos

    ras oncogenes in human cancer: A review

    Cancer Res.

    (1989)
  • V.L. Boyartchuk et al.

    Modulation of Ras and a-factor function by carboxyl-terminal proteolysis

    Science

    (1997)
  • Y. Chen et al.

    Solubilization, partial purification, and affinity labeling of the membrane-bound isoprenylated protein endoprotease

    Biochemistry

    (1996)
  • S. Clarke

    Protein isoprenylation and methylation at carboxyl-terminal cysteine residues

    Annu. Rev. Biochem.

    (1992)
  • J. Devereux et al.

    A comprehensive set of sequence analysis programs for the VAX

    Nucleic Acids Res.

    (1984)
  • K. Fujimura-Kamada et al.

    A novel membrane-associated metalloprotease, Ste24p, is required for the first step of NH2-terminal processing of the yeast a-factor precursor

    J. Cell Biol.

    (1997)
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    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession Nos. Y13834 and Y13835.

    1

    To whom correspondence should be addressed. Fax: 34–985–103564. E-mail: [email protected].

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