Granzyme B (GZMB) (GZMB)

Granzyme B (GZMB) is a potent serine protease primarily synthesized and stored in the cytotoxic granules of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) [UniProt P10144]. It serves as a critical effector molecule in the immune system's defense against tumors and viral infections by inducing rapid programmed cell death in target cells [PMID: 31435140]. Upon delivery into the target cell's cytosol via the pore-forming protein perforin, Granzyme B cleaves a specific set of intracellular substrates, most notably pro-caspase-3 and the BH3-only protein Bid, which triggers the mitochondrial apoptotic pathway [PMID: 20304837]. In the context of oncology, Granzyme B activity is a key determinant of the efficacy of immunotherapies, such as immune checkpoint inhibitors and CAR-T cell therapies, which rely on CTL-mediated killing [PMID: 28844836]. Beyond its role in apoptosis, Granzyme B can also cleave extracellular matrix proteins, contributing to tissue remodeling and inflammation in various chronic diseases [PMID: 25614318]. Therapeutic development focuses on both enhancing Granzyme B delivery to tumor cells using fusion proteins and inhibiting its activity to treat autoimmune and inflammatory conditions [PMID: 24655260].

Other names

GZMBGranzyme-2CTLA-1Cytotoxic T-lymphocyte proteinase 2Fragmentin-2Human lymphocyte proteinase

Granzyme B induces apoptosis by cleaving and activating pro-caspases (specifically Caspase-3 and Caspase-7) and the pro-apoptotic protein Bid, which leads to mitochondrial outer membrane permeabilization and subsequent DNA fragmentation [PMID: 20304837, PMID: 11048727].