Control of granzymes by serpins.
Although proteolysis mediated by granzymes has an important role in the immune response to infection or tumours, unrestrained granzyme activity may damage normal cells. In this review, we discuss the role of serpins within the immune system, as specific regulators of granzymes. The well-characterised human granzyme B-SERPINB9 interaction highlights the cytoprotective function that serpins have in safeguarding lymphocytes from granzymes that may leak from granules. We also discuss some of the pitfalls inherent in using rodent models of granzyme-serpin interactions and the ways in which our understanding of serpins can help resolve some of the current, contentious issues in granzyme biology.
Kaiserman
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Department of Biochemistry and Molecular Biology, Monash University, Building 77, Wellington Road, Clayton, Victoria 3800, Australia. dion.kaiserman@med.monash.edu.au
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D000818:Animals; D019610:Cytoprotection / Q000502:physiology*; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D012697:Serine Endopeptidases / Q000378:metabolism; D015843:Serpins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology*; D014764:Viral Proteins / Q000378:metabolism
D008565:Membrane Proteins; D015843:Serpins; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; C106610:Serpinb9 protein, mouse