Deletion of cysteine cathepsins B or L yields differential impacts on murine skin proteome and degradome

[en] Numerous studies highlight that concerted proteolysis is essential for skin morphology and function. The cysteine protease cathepsin L (Ctsl) has been implicated in epidermal proliferation and desquamation as well as in hair cycle regulation. In stark contrast, mice deficient for cathepsin B (Ctsb) do not display an overt skin phenotype. To understand the systematic consequences of deleting Ctsb or Ctsl, we determined protein abundances of > 1300 proteins and proteolytic cleavage events in skin samples of wild-type, Ctsb-/- and Ctsl-/- mice by mass spectrometry based proteomics. Both protease deficiencies revealed distinct quantitative changes in proteome composition. Ctsl-/- skin revealed increased levels of the cysteine protease inhibitors cystatin B and cystatin M/E, increased cathepsin D and accumulation of the extracellular glycoprotein periostin. Immunohistochemistry located periostin predominantly in hypodermal connective tissue of Ctsl-/- skin. Proteomic identification of proteolytic cleavage sites within skin proteins revealed numerous processing sites that are underrepresented in Ctsl-/- or Ctsb-/- samples. Notably, few of the affected cleavage sites shared the canonical Ctsl or Ctsb specificity, providing further evidence for a complex proteolytic network in the skin. Novel processing sites in proteins such as dermokine and Notch-1 were detected. Simultaneous analysis of acetylated protein N-termini showed prototypical mammalian N-alpha acetylation. These results illustrate an influence of both Ctsb and Ctsl on the murine skin proteome and degradome with the phenotypic consequences of the absence of either protease differing considerably.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Tholen, Stefan

Biniossek, Martin L

Gansz, Martina

Gomez-Auli, Alejandro

Werner, Fee

Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme

Kizhakkedathu, Jayachandran N

Boerries, Melanie

Busch, Hauke

Reinheckel, Thomas

Schilling, Oliver

Language :

English

Title :

Deletion of cysteine cathepsins B or L yields differential impacts on murine skin proteome and degradome

Publication date :

2013

Journal title :

Molecular and Cellular Proteomics

ISSN :

1535-9476

eISSN :

1535-9484

Publisher :

American Society for Biochemistry and Molecular Biology, Bethesda, United States - Maryland

Volume :

Issue :

Pages :

611-25

Peer reviewed :

Peer Reviewed verified by ORBi

European Projects :

FP7 - 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.

Funders :

CE - Commission Européenne

Available on ORBi :

since 16 January 2013

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