Cross-Talk between Two Cysteine Protease Families

By T. Nakagawa, Junying Yuan. Journal of Cell Biology, 2000

654 citations recorded by the source corpus.

Calpains and caspases are two cysteine protease families that play important roles in regulating pathological cell death. Here, we report that m-calpain may be responsible for cleaving procaspase-12, a caspase localized in the ER, to generate active caspase-12. In addition, calpain may be responsible for cleaving the loop region in Bcl-xL and, therefore, turning an antiapoptotic molecule into a proapoptotic molecule. We propose that disturbance to intracellular calcium storage as a result of ischemic injury or amyloid β peptide cytotoxicity may induce apoptosis through calpain- mediated caspase-12 activation and Bcl-xL inactivation. These data suggest a novel apoptotic pathway involving calcium-mediated calpain activation and cross-talks between calpain and caspase families.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/85b5010bca0b1fdaaa2bd0dc1ec9fa19aedc090c

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Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis (2003, background): “1-t-caspase 12) were previously described (Nakagawa and Yuan, 2000).”
Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival (2008, background): “Despite many of the initiating events occurring at intracellular membranes, increases in [Ca 2+ ] i can also activate death effectors in the cytosol, including calpains, which are potent amplifiers and initiators of death signallin”
Regulation of apoptosis by endoplasmic reticulum pathways (2003, background): “In vitro, m-calpain cleaved caspase-12 at T132 and K158, which releases the prodomain from the catalytic subunits and increases enzymatic activity (Nakagawa and Yuan, 2000).”
Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis (2008, background): “In contrast, Bcl-XL enhanced spontaneous [Ca 2þ ]c signaling in all three IP3R isoform-expressing cell lines.”
β-Cell death during progression to diabetes (2001, background): “Also involved in this pathway are IRE-1, TRAF-2, calpain, caspase-7 and perhaps caspase-9 (ref”
A trip to the ER: coping with stress. (2004, background): “The regulation of calcium concentrations in the ER, mitochondria and cytoplasm might represent an additional trigger of apoptosis (Figure 3). Indeed, some data suggest that calcium regulation is required even for the activation of the caspase-12 pathway, because caspase- 12 activation might occur th”
A decade of caspases (2003, background): “The Ca2þ-activated protease m-calpain can process caspase-12 following ER stress (Nakagawa and Yuan, 2000), whereas the lysosomal protease cathepsin B was shown to process caspase-1 and -11 in vitro (Schotte et al., 1998; Vancompernolle et al., 1998).”