biostudies-literatureMadzharova EProfessor Ulrich auf dem Keller's Novo Nordisk Foundation Young Investigator AwardPRO-MS: Danish National Mass Spectrometry Platform for Functional ProteomicsDanish Cancer Society Foundatione5128https://www.ebi.ac.uk/biostudies/studies/S-EPMC11285871biostudies-literatureUnknown33(8)Extracellular proteolysis critically regulates cellular and tissue responses and is often dysregulated in human diseases. The crosstalk between proteolytic processing and other major post-translational modifications (PTMs) is emerging as an important regulatory mechanism to modulate protease activity and maintain cellular and tissue homeostasis. Here, we focus on matrix metalloproteinase (MMP)-mediated cleavages and N-acetylgalactosamine (GalNAc)-type of O-glycosylation, two major PTMs of proteins in the extracellular space. We investigated the influence of truncated O-glycan trees, also referred to as Tn antigen, following the inactivation of C1GALT1-specific chaperone 1 (COSMC) on the general and MMP9-specific proteolytic processing in MDA-MB-231 breast cancer cells. Quantitative assessmProtein science : a publication of the Protein SocietySubstrate O-glycosylation actively regulates extracellular proteolysis.PMC11285871R302-A176185072-00007BNNF16OC0020670Kalogeropoulos KAuf dem Keller UMadzharova EFrancavilla CSabino FfalseSubstrate O-glycosylation actively regulates extracellular proteolysis.Extracellular proteolysis critically regulates cellular and tissue responses and is often dysregulated in human diseases. The crosstalk between proteolytic processing and other major post-translational modifications (PTMs) is emerging as an important regulatory mechanism to modulate protease activity and maintain cellular and tissue homeostasis. Here, we focus on matrix metalloproteinase (MMP)-mediated cleavages and N-acetylgalactosamine (GalNAc)-type of O-glycosylation, two major PTMs of proteins in the extracellular space. We investigated the influence of truncated O-glycan trees, also referred to as Tn antigen, following the inactivation of C1GALT1-specific chaperone 1 (COSMC) on the general and MMP9-specific proteolytic processing in MDA-MB-231 breast cancer cells. Quantitative assessm2024-01-01T00:00:00Z2024 Aug2026-06-03T00:19:01.091Z2026-04-22T03:11:30.501ZS-EPMC112858713907426110.1002/pro.5128