biostudies-literatureTholen SEuropean Research Council611-25https://www.ebi.ac.uk/biostudies/studies/S-EPMC3591655biostudies-literatureUnknown12(3)Numerous studies highlight the fact 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 in cathepsin B (Ctsb) do not display an overt skin phenotype. To understand the systematic consequences of deleting Ctsb or Ctsl, we determined the protein abundances of >1300 proteins and proteolytic cleavage events in skin samples of wild-type, Ctsb(-/-), and Ctsl(-/-) mice via 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,Molecular & cellular proteomics : MCPDeletion of cysteine cathepsins B or L yields differential impacts on murine skin proteome and degradome.PMC3591655282111Kizhakkedathu JNReinheckel TBoerries MBusch HBiniossek MLTholen SGansz MGomez-Auli ANoel ASchilling OBengsch FfalseDeletion of cysteine cathepsins B or L yields differential impacts on murine skin proteome and degradome.Numerous studies highlight the fact 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 in cathepsin B (Ctsb) do not display an overt skin phenotype. To understand the systematic consequences of deleting Ctsb or Ctsl, we determined the protein abundances of >1300 proteins and proteolytic cleavage events in skin samples of wild-type, Ctsb(-/-), and Ctsl(-/-) mice via 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,2013-01-01T00:00:00Z2013 Mar2026-05-01T05:08:23.078Z2026-04-07T16:40:55.655ZS-EPMC35916552323344810.1074/mcp.m112.01796210.1074/mcp.M112.017962