Granzyme B gene is mapped onchromosome 14q.11.2 with 3.2kb long consisting of 4 introns and 5 exons that is believed to evolve from granzyme H. This enzyme is primarily as inactive precursor zymogen form with amino terminal peptide sequence cleaved by cathepsin C.
Granzyme B is shown to induced cytotoxic T lymphocytes mediated target cell DNA fragmentation and apoptosis in which once released it binds to the receptor mannose-6-phosphate or insulin-like growth factor II receptor which then endocytosed yet hang about in endocytic vesicles awaiting for perforin to release targeting caspase-3 straight through themitochondria beginning caspase cascade to DNA. Caspase activity is needed in apoptosis however Granzyme B can still initiate mitochondrial actions through cleavage in the absence of caspase activity.
Granzyme B has been valuable in diagnosing natural killer cell as well as anaplastic large cell lymphoma in which high level of cytotoxic T cells reveals to be adverse prognostic indicator in Hodgkin’s disease. It also acts at multiple points to initiate the death of the offending cell that shows importance in internal signaling pathways which may lead to significant advances in cell transplantation and cancer therapy.
Gene name: GZMB
Protein name: Granzyme B