title: Cytohesin-associated scaffolding protein (CASP) is a substrate for granzyme B and ubiquitination.
abstract: Natural killer (NK) cells are a sub-population of cytotoxic lymphocytes that can kill tumor or infected cells without prior exposure, by secreting the contents of preformed cytotoxic vesicles, containing perforin and granzymes, at the immune synapse. Cytohesin-associated scaffolding protein (CASP) is an adaptor molecule uniquely expressed in lymphocytes that forms complexes with both vesicle-initiating and sorting proteins, and has roles in NK cell migration, cytotoxicity, and cytokine secretion. In this study, we show that CASP contains a conserved granzyme B cleavage site that could modify its intracellular localization and interaction with sorting nexin 27. We also provide evidence that CASP is modified by ubiquitination. Both of these post-translational modifications could rapidly modify CASP function and highlight the dynamic regulatory mechanisms that direct its role in NK cell functions.
authors.affiliation: Department of Biology, Dalhousie University, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Tompkins
authors.affiliation: Department of Health Sciences, Brock University, Canada.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: MacNeil
authors.affiliation: Department of Biology, Dalhousie University, Canada. Electronic address: bill.pohajdak@dal.ca.
authors.forename: Bill
authors.initials: B
authors.lastname: Pohajdak
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002457:Cell Extracts / Q000737:chemistry; D002460:Cell Line; D005786:Gene Expression Regulation; D053804:Granzymes / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors; D054875:Ubiquitination
chemical_list: C080632:CUX1 protein, human; D002457:Cell Extracts; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D053804:Granzymes
keywords: CASP; Granzyme B; NK cell; Ubiquitination