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The Proprotein Convertases Furin and PACE4 Play a Significant Role in Tumor Progression

2000; Wiley; Volume: 28; Issue: 2 Linguagem: Inglês

10.1002/1098-2744(200006)28

1098-2744

Daniel E. Bassi, Haleh Mahloogi, Andr�s J. P. Klein-Szanto,

Cellular transport and secretion

Molecular CarcinogenesisVolume 28, Issue 2 p. 63-69 In Perspective The Proprotein Convertases Furin and PACE4 Play a Significant Role in Tumor Progression† Daniel E. Bassi, Daniel E. Bassi Department of Pathology, Fox Chase Cancer Center, Philadelphia, PennsylvaniaSearch for more papers by this authorHaleh Mahloogi, Haleh Mahloogi Department of Pathology, Fox Chase Cancer Center, Philadelphia, PennsylvaniaSearch for more papers by this authorAndrés J. P. Klein-Szanto, Corresponding Author Andrés J. P. Klein-Szanto [email protected] Department of Pathology, Fox Chase Cancer Center, Philadelphia, PennsylvaniaDepartment of Pathology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19006.Search for more papers by this author Daniel E. Bassi, Daniel E. Bassi Department of Pathology, Fox Chase Cancer Center, Philadelphia, PennsylvaniaSearch for more papers by this authorHaleh Mahloogi, Haleh Mahloogi Department of Pathology, Fox Chase Cancer Center, Philadelphia, PennsylvaniaSearch for more papers by this authorAndrés J. P. Klein-Szanto, Corresponding Author Andrés J. P. Klein-Szanto [email protected] Department of Pathology, Fox Chase Cancer Center, Philadelphia, PennsylvaniaDepartment of Pathology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19006.Search for more papers by this author First published: 14 July 2000 https://doi.org/10.1002/1098-2744(200006)28:2 3.0.CO;2-CCitations: 63 † Special Editor: Claudio J. Conti AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Processing of latent precursor proteins by proprotein convertases (PCs) into their biologically active products is a common mechanism required for many important biologic functions. This process is tightly regulated, leading to the generation of active peptides and proteins including neuropeptides and polypeptide hormones, protein tyrosine phosphatases, growth factors and their receptors, and enzymes including matrix metalloproteases (MMPs). These processing reactions occurs at pairs of basic amino acids. Within the past several years, a novel family of Ca2+-dependent serine proteases has been identified, all of which possess homology to the endoproteases subtilisin (bacteria) and kexin (yeast). This family of PCs is currently comprised of fewer than a dozen members, known as furin/paired basic amino-acid–cleaving enzyme (PACE), PC1/PC3, PC2, PC4, PACE4, PC5/PC6, and PC7/PC8/lymphoma proprotein convertase. They share a high degree of amino-acid identity of 50–75% within their catalytic domains. Despite the relatively high degree of homology in the PC family, only PACE4 and furin localize to the same chromosome: mouse chromosome 7 and human chromosome 15. Recent reports have supported a possible functional role for PCs in tumorigenesis. For instance, convertases have been shown to be expressed in various tumor lines and human primary tumors. Furin and PACE4 process stromelysin 3 (MMP-11 or Str-3), an MMP involved in tumor invasion, into its mature, active form. 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