Identification of PCPE-2 as the endogenous specific inhibitor of human BMP-1/tolloid-like proteinases

Vadon-Le Goff S, Tessier A, Napoli M, Dieryckx C, Bauer J, Dussoyer M, Lagoutte P, Peyronnel C, Essayan L, Kleiser S, Tueni N, Bettler E, Mariano N, Errazuriz-Cerda E, Fruchart Gaillard C, Ruggiero F, Becker-Pauly C, Allain JM, Bruckner-Tuderman L, Nyström A, Moali C (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 14

Article Number: 8020

Journal Issue: 1

DOI: 10.1038/s41467-023-43401-0

Abstract

BMP-1/tolloid-like proteinases (BTPs) are major players in tissue morphogenesis, growth and repair. They act by promoting the deposition of structural extracellular matrix proteins and by controlling the activity of matricellular proteins and TGF-β superfamily growth factors. They have also been implicated in several pathological conditions such as fibrosis, cancer, metabolic disorders and bone diseases. Despite this broad range of pathophysiological functions, the putative existence of a specific endogenous inhibitor capable of controlling their activities could never be confirmed. Here, we show that procollagen C-proteinase enhancer-2 (PCPE-2), a protein previously reported to bind fibrillar collagens and to promote their BTP-dependent maturation, is primarily a potent and specific inhibitor of BTPs which can counteract their proteolytic activities through direct binding. PCPE-2 therefore differs from the cognate PCPE-1 protein and extends the possibilities to fine-tune BTP activities, both in physiological conditions and in therapeutic settings.

Involved external institutions

Christian-Albrechts-Universität zu Kiel DE Germany (DE) Solids Mechanic Laboratory / Laboratoire Mécanique des Solides (LMS) FR France (FR) Universitätsklinikum Freiburg DE Germany (DE) Université de Lyon (UDL) FR France (FR) Université Paris-Saclay FR France (FR) École normale supérieure de Lyon (ENS) FR France (FR)

How to cite

APA:

Vadon-Le Goff, S., Tessier, A., Napoli, M., Dieryckx, C., Bauer, J., Dussoyer, M.,... Moali, C. (2023). Identification of PCPE-2 as the endogenous specific inhibitor of human BMP-1/tolloid-like proteinases. Nature Communications, 14(1). https://dx.doi.org/10.1038/s41467-023-43401-0

MLA:

Vadon-Le Goff, Sandrine, et al. "Identification of PCPE-2 as the endogenous specific inhibitor of human BMP-1/tolloid-like proteinases." Nature Communications 14.1 (2023).

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