PCPE-2 (procollagen C-proteinase enhancer-2): The non-identical twin of PCPE-1

• Published in: Matrix biology 2024-12, Vol.134, p.59-78
• Main Authors: Napoli, Manon, Bauer, Julien, Bonod, Christelle, Vadon-Le Goff, Sandrine, Moali, Catherine
• Format: Article
• Language: English
• Subjects: Animals; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Bone Morphogenetic Protein 1 - genetics; Bone Morphogenetic Protein 1 - metabolism; Cancer; Collagen; Collagen - genetics; Collagen - metabolism; Extracellular Matrix Proteins; Humans; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inhibition; Life Sciences; Lipid metabolism; Metalloprotease; Tolloid-Like Metalloproteinases - genetics; Tolloid-Like Metalloproteinases - metabolism
• ISSN: 0945-053X; 1569-1802; 1569-1802
• DOI: 10.1016/j.matbio.2024.09.001

•PCPE-1 and PCPE-2 share high structural similarity.•PCPE-2 is described as an enhancer of collagen proteolytic maturation like PCPE-1.•PCPE-2 differs from PCPE-1 by its ability to inhibit BMP-1 and tolloid proteinases.•The two proteins have different expression patterns in normal and disease tissues.•PCPE-2 also regulates lipid metabolism and innate immunity. PCPE-2 was discovered at the beginning of this century, and was soon identified as a close homolog of PCPE-1 (procollagen C-proteinase enhancer 1). After the demonstration that it could also stimulate the proteolytic maturation of fibrillar procollagens by BMP-1/tolloid-like proteinases (BTPs), PCPE-2 did not attract much attention as it was thought to fulfill the same functions as PCPE-1 which was already well-described. However, the tissue distribution of PCPE-2 shows both common points and significant differences with PCPE-1, suggesting that their activities are not fully overlapping. Also, the recently established connections between PCPE-2 (gene name PCOLCE2) and several important diseases such as atherosclerosis, inflammatory diseases and cancer have highlighted the need for a thorough reappraisal of the in vivo roles of this regulatory protein. In this context, the recent finding that, while retaining the ability to bind fibrillar procollagens and to activate their C-terminal maturation, PCPE-2 can also bind BTPs and inhibit their activity has substantially extended its potential functions. In this review, we describe the current knowledge about PCPE-2 with a focus on collagen fibrillogenesis, lipid metabolism and inflammation, and discuss how we could further advance our understanding of PCPE-2-dependent biological processes.