Granzyme B intracellular substrates (GZMB substrates)

Granzyme B (GZMB) intracellular substrates are a diverse group of proteins targeted by the serine protease Granzyme B to induce apoptosis in compromised cells. Upon delivery into the cytoplasm by cytotoxic T lymphocytes or natural killer cells via perforin-mediated pores, GZMB cleaves specific substrates such as Bid, Caspase-3, and ICAD (PMID: 11526524). The cleavage of Bid into truncated Bid (tBid) triggers mitochondrial outer membrane permeabilization, while the direct activation of executioner caspases ensures the rapid and systematic dismantling of the cell (PMID: 15123777). This proteolytic activity is a cornerstone of the adaptive immune response against tumors and intracellular pathogens (UniProt P10144). However, aberrant GZMB activity is associated with various inflammatory and autoimmune conditions, where it causes unintended tissue damage. While GZMB itself is the primary therapeutic target for modulation, its substrates serve as essential biomarkers for monitoring cytotoxic activity and drug efficacy in clinical settings.

Other names

Granzyme B targetsGZMB proteolytic substratesPro-apoptotic substrates of Granzyme BCytotoxic T lymphocyte-mediated apoptotic substrates

Granzyme B cleaves these substrates at specific aspartic acid residues (P1 position), triggering a cascade that activates executioner caspases and induces mitochondrial dysfunction to execute programmed cell death.