Cathepsin V: Molecular characteristics and significance in health and disease
Graphical abstract
Introduction
Cathepsin V (cathepsin L2, EC 3.4.22.43) is a lysosomal cysteine protease related to papain from Carica papaya (C1 family, clan CA; MEROPS protease classification system, Rawlings et al., 2018) and is part of the eleven cysteine cathepsins (B, C, F, H, K, L, O, S, V, W, X/Z) present in humans. This protease has been discovered (as cathepsins K, S, X/Z, F, O, and W) in the 1990s, later than cathepsin C which was identified in the 1940s, and cathepsins B, H and L which were characterized during the second half of the previous century (Greenbaum and Fruton, 1957; Kirschke et al., 1979). Nevertheless, cathepsin V is currently gaining a growing interest according to its diverse roles in physiological and pathological processes, including MHC class II-restricted antigen presentation, corneal neovascularization, vascular diseases, or cancers. In this review, we summarize molecular characteristics and functional properties of cathepsin V in health and disease covering over twenty years of research.
Section snippets
Nomenclature, genomic organization, and gene expression
Human cathepsin V (also originally designated as cathepsin U) was first cloned from cDNA libraries derived from the corneal epithelium, thymus, and testis, by three independent research groups (Adachi et al., 1998; Santamaría et al., 1998; Brömme et al., 1999). Cathepsin V gene (CTSL2/CTSV) was localized by FISH analysis on the long arm of human chromosome 9q22.2, a site adjacent to the cathepsin L locus (CTSL1) (Itoh et al., 1999). Except for cathepsin B gene that is present on the short arm
Cornea
Keratoconus corneas (KC) is an eye disorder (blurred vision, increased sensitivity to bright light and glare) resulting in a progressive thinning of the cornea likely due to collagen deficiency in cornea, associated with oxidative stress. It was proposed that the proteolytic degradation of some BM constituents (i.e., fibronectin, laminins, collagens, and proteoglycans) may be related, in concert with other thiol-dependent cathepsins, to an increase of cathepsin V mRNA expression and its
Concluding remarks
This review aims to summarize current knowledge on cysteine cathepsin V, covering from its discovery in the late nineties to latest advances exploring cathepsin V expression (tissue and cellular distribution), enzymatic activity, and regulation by protein inhibitors and non-proteinogenic effectors. Although cathepsin V is still less characterized and investigated than some counterparts, i.e., cathepsins B, C, K, L, and S, there are increasing clues that cathepsin V plays a pivotal role in a
Author contributions
F.L. drafted the review article; F.L. and G.L. wrote the article; F.L. coordinated the writing of the review; T.C. and F.L. prepared the tables and the figures; T.C., G.L., and F.L. participated in bibliographic research; T.C. and A.S. edited the article. All authors have read and agreed to the published version of the manuscript.
Declaration of competing interest
The authors declare no conflict of interest. The funding sources had no role in the writing of the manuscript.
Acknowledgments
We acknowledge the University of Tours and the Institut National de la Santé et de la Recherche Médicale (INSERM) for institutional funding, and la Région Centre-Val de Loire, France (Pirana project; number 2019–00134916). Dr Thibault Chazeirat is a former recipient of a doctoral grant from the Ministère de l’Enseignement Supérieur, de la Recherche, et de l’Innovation (MESRI), France.
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