cFLIP L protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation

Autor:	Alexander Poltorak, Hayley I. Muendlein, Wilson M. Connolly, Zoie Magri, David Jetton, Keith P. Eidell, Irina Smirnova
Rok vydání:	2020
Předmět:	0301 basic medicine Gene isoform Programmed cell death Multidisciplinary Lipopolysaccharide Pyroptosis Inflammation In vitro Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry In vivo 030220 oncology & carcinogenesis medicine Secretion medicine.symptom
Zdroj:	Science. 367:1379-1384
ISSN:	1095-9203 0036-8075
Popis:	Macrophages cFLIP out Pathogens have evolved to survive within hosts in part by interfering with host signaling cascades. Yersinia bacteria use the effector protein YopJ to thwart MAP kinase signaling downstream of Toll-like receptor activation. In response to YopJ, host cells can release interleukin-1β and initiate pyroptosis by inhibition of the kinase TAK1 and subsequent caspase-8–directed cleavage of gasdermin D, a protein that forms cell membrane pores. Muendlein et al. report that cFLIP, a major antiapoptotic regulator, plays a central role in this process. Knockdowns of the long but not short cFLIP isoform in macrophages removes the requirement for TAK1 inhibition. Rather, deficiency of the long isoform fuels caspase-8 activation, mitochondrial complex II formation, pyroptosis, and interleukin-1β secretion in response to lipopolysaccharide alone, underscoring its importance for cell death and inflammation. Science , this issue p. 1379
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::aa130518942ad7f7b4e9bcf5841171db https://doi.org/10.1126/science.aay3878 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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