The M476W/Q482H mutation of procaspase-8 restored caspase-8-mediated apoptosis

Add time:09/01/2019    Source:sciencedirect.com

Caspase-8 is an initiator of apoptotic signalling, and aberrations in procaspase-8 have been verified to be associated with malignant tumours. In previous studies, various procaspase-8 mutants were identified in AML patients, such as Q482H and M476W/Q482H mutations. The Q482H mutation can abolish caspase-8-mediated apoptosis by attenuating the dimerization of procaspase-8 protein monomers, causing AML patients carrying the Q482H mutation to develop resistance to chemotherapeutics. The patients with the M476W/Q482H mutation were sensitive to chemotherapy. Nevertheless, the underlying molecular mechanism is still unclear in regard to how the M476W/Q482H mutation restored caspase-8-mediated apoptosis. In this study, apoptosis was detected in the cells overexpressing the WT or mutant procaspase-8 with or without TRAIL treatment. Western blotting was devoted to detect the cleavage of procaspase-8 or the expression of proteins downstream in the apoptotic cascade and CO-IP was employed to analyze the dimerization of WT and mutant procaspase-8 proteins. Results demonstrated cells carrying the M476W/Q482H mutation restored caspase-8-mediated and TRAIL-induced apoptosis. The M476W/Q482H mutation recovered the dimerization of procaspase-8. Taken together, the M476W/Q482H mutation have restored caspase-8-mediated apoptosis resulting from the recovery of procaspase-8 dimerization.

We also recommend Trading Suppliers and Manufacturers of N(8)-norphysostigmine (cas 19573-10-5). Pls Click Website Link as below: cas 19573-10-5 suppliers

Prev:Improving the pervaporation performance of PDMS membranes for n-butanol by incorporating silane-modified ZIF-8 particles
Next:Fluorometric determination of nitrite in natural waters with 3-aminonaphthalene-1,5-disulphonic acid by flow-injection analysis)