Granzyme B directly and efficiently cleaves several downstream caspase substrates: implications for CTL-induced apoptosis.
AuthorsAndrade F, Roy S, Nicholson D, Thornberry N, Rosen A, Casciola-Rosen L
JournalImmunity
PubMed ID9586635
'Caspase-mediated proteolysis of downstream substrates is a critical element of the execution pathway common to all forms of apoptosis studied to date. While this caspase-dependent pathway is activated during cytotoxic lymphocyte granule-induced cell death, recent studies have also provided evidence for caspase-independent pathways. However, the mechanisms mediating these additional pathways ... More
Granzyme B delivery via perforin is restricted by size, but not by heparan sulfate-dependent endocytosis.
AuthorsKurschus FC, Fellows E, Stegmann E, Jenne DE
JournalProc Natl Acad Sci U S A
PubMed ID18772390
'How granzymes gain entry into the cytosol of target cells during killer cell attack has been the subject of several studies in the past, but the effective delivery mechanism during target cell encounter has not been clarified. Here we show that granzyme B (GzmB) mutants lacking binding to negatively charged, ... More
Granzyme B: pro-apoptotic, antiviral and antitumor functions.
AuthorsTrapani JA, Sutton VR
JournalCurr Opin Immunol
PubMed ID14499262
'Granzyme B is a caspase-like serine protease that is released by cytotoxic lymphocytes to kill virus-infected and tumor cells. Major recent advances in our understanding of granzyme B biochemistry, biology and function include an appreciation of its uptake into and trafficking within target cells, a thorough dissection of how cell ... More
Granzyme B-mediated apoptosis proceeds predominantly through a Bcl-2-inhibitable mitochondrial pathway.
AuthorsPinkoski MJ, Waterhouse NJ, Heibein JA, Wolf BB, Kuwana T, Goldstein JC, Newmeyer DD, Bleackley RC, Green DR
JournalJ Biol Chem
PubMed ID11278459
Cytotoxic T lymphocytes kill virus-infected and tumor cell targets through the concerted action of proteins contained in cytolytic granules, primarily granzyme B and perforin. Granzyme B, a serine proteinase with substrate specificity similar to the caspase family of apoptotic cysteine proteinases, is capable of cleaving and activating a number of ... More