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Granzyme B

Definition:

Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse. It cleaves after Asp. Once delivered into the target cell, acts by catalyzing cleavage of gasdermin-E (GSDME), releasing the pore-forming moiety of GSDME, thereby triggering pyroptosis and target cell death. Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution. Cleaves caspase-3, -9 and -10 (CASP3, CASP9 and CASP10, respectively) to give rise to active enzymes mediating apoptosis. Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair (By similarity).

References:

[1]. Zhibin Zhang, et al. Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature. 2020 Mar;579(7799):415-420. [Content Brief]

[2]. A Hameed, et al. Characterization of three serine esterases isolated from human IL-2 activated killer cells. J Immunol. 1988 Nov 1;141(9):3142-7. [Content Brief]

[3]. C J Froelich, et al. Human granzyme B degrades aggrecan proteoglycan in matrix synthesized by chondrocytes. J Immunol. 1993 Dec 15;151(12):7161-71. [Content Brief]

[4]. Yuying Liu, et al. Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome. Sci Immunol. 2020 Jan 17;5(43):eaax7969. [Content Brief]

[5]. O Krähenbühl, et al. Characterization of granzymes A and B isolated from granules of cloned human cytotoxic T lymphocytes. J Immunol. 1988 Nov 15;141(10):3471-7. [Content Brief]

[6]. X Yang, et al. Granzyme B mimics apical caspases. Description of a unified pathway for trans-activation of executioner caspase-3 and -7. J Biol Chem. 1998 Dec 18;273(51):34278-83. [Content Brief]

[7]. M Poe, et al. Human cytotoxic lymphocyte granzyme B. Its purification from granules and the characterization of substrate and inhibitor specificity. J Biol Chem. 1991 Jan 5;266(1):98-103. [Content Brief]

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