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Processing of human cathepsin D is independent of its catalytic function and auto-activation: involvement of cathepsins L and B.

Abstract : The current mechanism proposed for the processing and activation of the 52 kDa lysosomal aspartic protease cathepsin D (cath-D) is a combination of partial auto-activation generating a 51 kDa pseudo-cath-D, followed by enzyme-assisted maturation involving cysteine and/or aspartic proteases and yielding successively a 48 kDa intermediate and then 34 + 14 kDa cath-D mature species. Here we have investigated the in vivo processing of human cath-D in a cath-D-deficient fibroblast cell line in order to determine whether its maturation occurs through already active cath-D and/or other proteases. We demonstrate that cellular cath-D is processed in a manner independent of its catalytic function and that auto-activation is not a required step. Moreover, the cysteine protease inhibitor E-64 partially blocks processing, leading to accumulation of 52-48 kDa cath-D intermediates. Furthermore, two inhibitors, CLICK148 and CA-074Met, specific for the lysosomal cath-L and cath-B cysteine proteases induce accumulation of 48 kDa intermediate cath-D. Finally, maturation of endocytosed pro-cath-D is also independent of its catalytic function and requires cysteine proteases. We therefore conclude that the mechanism of cath-D maturation involves a fully-assisted processing similar to that of pro-renin.
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https://www.hal.inserm.fr/inserm-00153742
Contributor : Yves Le Ster <>
Submitted on : Monday, June 11, 2007 - 5:45:23 PM
Last modification on : Wednesday, October 11, 2017 - 1:02:01 AM
Long-term archiving on: : Thursday, April 8, 2010 - 5:19:22 PM

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Valérie Laurent-Matha, Danielle Derocq, Christine Prébois, Nobuhiko Katunuma, Emmanuelle Liaudet-Coopman. Processing of human cathepsin D is independent of its catalytic function and auto-activation: involvement of cathepsins L and B.. Journal of Biochemistry, Oxford University Press (OUP), 2006, 139 (3), pp.363-71. ⟨10.1093/jb/mvj037⟩. ⟨inserm-00153742⟩

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