Human genome encodes six paralogous gasdermin genes:GSDMA,GSDMB,GSDMC,GSDMD,GSDME and DFNB59.1 Proteolytic cleavage of these gasdermin proteins liberates an N-terminal(NT)fragment from autoinhibition,which assembles i...Human genome encodes six paralogous gasdermin genes:GSDMA,GSDMB,GSDMC,GSDMD,GSDME and DFNB59.1 Proteolytic cleavage of these gasdermin proteins liberates an N-terminal(NT)fragment from autoinhibition,which assembles in membrane to form pores and execute pyroptotic cell death in general.1 In contrast to other gasdermins,gasdermin B(GSDMB)is the only gasdermin gene that has not been identified in rodents.Zhou et al first shed light on the molecular mechanism by which cytotoxic lymphocyte-derived granzyme A(GZMA)cleaves GSDMB to execute pyroptosis in GSDMB-positive cells,especially in cancer cells.2 In this issue of Cell,Hansen et al reported a dynamic host pathogen S.flexneri prevents GSDMB-mediated lysis by secreting IpaH7.8,which targets and ubiquitinates GSDMB for 26S proteasome destruction.3 They showed that GSDMB implements bacteriocidic ability by recognition of the phospholipids on Gram-negative bacterial membranes rather than lysing host cells.Although their experimental design and data are clearly presented and straightforward,there are still some doubts to be clarified.展开更多
基金The work was supported by the National Natural Science Foundation of China(No.82072223)Scientific Research Foundation of Graduate School of Southeast University(No.YBPY2172)+1 种基金333 High Level Talents Training Project of Jiangsu Province(No.BRA2019011)General Project of Military Logistics Research(No.CLB19J025).
文摘Human genome encodes six paralogous gasdermin genes:GSDMA,GSDMB,GSDMC,GSDMD,GSDME and DFNB59.1 Proteolytic cleavage of these gasdermin proteins liberates an N-terminal(NT)fragment from autoinhibition,which assembles in membrane to form pores and execute pyroptotic cell death in general.1 In contrast to other gasdermins,gasdermin B(GSDMB)is the only gasdermin gene that has not been identified in rodents.Zhou et al first shed light on the molecular mechanism by which cytotoxic lymphocyte-derived granzyme A(GZMA)cleaves GSDMB to execute pyroptosis in GSDMB-positive cells,especially in cancer cells.2 In this issue of Cell,Hansen et al reported a dynamic host pathogen S.flexneri prevents GSDMB-mediated lysis by secreting IpaH7.8,which targets and ubiquitinates GSDMB for 26S proteasome destruction.3 They showed that GSDMB implements bacteriocidic ability by recognition of the phospholipids on Gram-negative bacterial membranes rather than lysing host cells.Although their experimental design and data are clearly presented and straightforward,there are still some doubts to be clarified.
