UVB-induced regulated necrosis is followed by autophagy and caspase activation only when FADD is deficient (CROSBI ID 640096)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Antunovic, Maja ; Caput Mihalic, Katarina ; Pusic, Maja ; Marijanovic, Inga
engleski
UVB-induced regulated necrosis is followed by autophagy and caspase activation only when FADD is deficient
Research during the last decade clearly illustrates the important contribution of alternative forms of cell death in development, homeostasis and pathogenesis. Fas-associated protein with death domain (FADD) is critical adaptor protein for death receptor-mediated apoptosis. Recent evidence suggested negative roles of FADD in RIP1- and RIP3-dependent necroptosis. Since necroptosis can be initiated by various stimuli in a variety of cell types independently of death receptors, the exact mechanisms and functions of FADD require further investigation. Based on the presumption that FADD protein intermediates apoptotic, as well as necroptotic and autophagic signals after exposure to NB-UVB irradiation, we tested its role of death adaptor using FADD knockout mouse embryonic fibroblasts and specific inhibitors, Necrostatin- 1 and pan-caspase inhibitor zVAD-fmk. The results show that wild type mouse embryonic fibroblast die by triggering apoptotic death signals through mitochondrial control, but independently of p53. FADD knockout mouse embryonic fibroblasts die by regulated necrosis and autophagy, by activating caspase-3 and -9. Their necrotic program does not involve p53 nor Bax and Bcl-2. The results show that protein FADD as well as RIP1 are essential for triggering apoptotic cell death after NB-UVB irradiation. FADD protein acts as negative regulator of necroptosis followed by autophagy.
regulated necrosis; autophagy; FADD; UVB
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Podaci o prilogu
2016.
objavljeno
Podaci o matičnoj publikaciji
Podaci o skupu
EMBO Conference on translational research in cancer cell metabolism
poster
04.10.2016-06.10.2016
Bilbao, Španjolska