Dataset Information

The autophagic protein FYCO1 controls TRAIL receptor induced apoptosis and is inactivated by caspase 8

ABSTRACT: Apoptosis and autophagy are programs of controlled cellular suicide or survival, closely interconnected at multiple levels to ensure balanced answers to stress signals, and often dysregulated in cancer. Here, we identified FYCO1, a protein that promotes microtubule plus end–directed transport of autophagic and endosomal vesicles as molecular interaction partner of activated caspase 8. The absence of FYCO1 sensitized cells to basal and TRAIL induced apoptosis by receptor accumulation and stabilization of the Death Inducing Signaling Complex (DISC), caused by defective interaction with the CCZ1-MON1A complex, necessary to activate RAB7A and allow proper endosome/autophagosome maturation and fusion with lysosomes. We demonstrated that FYCO1 is a novel and specific caspase 8 substrate, and that the cleavage at aspartate 1306 inactivates its function, allowing for the progression of apoptosis. Furthermore, a lack of FYCO1 resulted in a more efficient and prolonged formation of the TNF-R signaling complex. Thus, FYCO1 limits the ligand-induced and steady-state signaling of TNFR-superfamily members, providing a natural control mechanism that fine tunes both apoptotic and inflammatory answers.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Uwe Warnken

LAB HEAD: Uwe Warnken

PROVIDER: PXD033760 | Pride | 2023-10-24

REPOSITORIES: Pride

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			Action	DRS
	mqpar.xml	Xml
	oecf1-210615-UW3118-pp_A1.raw	Raw
	oecf1-210615-UW3118-pp_A2.raw	Raw
	oecf1-210615-UW3118-pp_A3.raw	Raw
	oecf1-210615-UW3118-pp_B1.raw	Raw

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The autophagic protein FYCO1 controls TNFRSF10/TRAIL receptor induced apoptosis and is inactivated by CASP8 (caspase 8).

Coppola Valeria V Marino Ilaria I Warnken Uwe U Falchi Mario M Pasquini Luca L Biffoni Mauro M De Maria Ruggero R Haas Tobias Longin TL

Autophagy 20230707 10

Apoptosis is a tightly controlled cell death program executed by proteases, the so-called caspases. It plays an important role in tissue homeostasis and is often dysregulated in cancer. Here, we identified FYCO1, a protein that promotes microtubule plus end-directed transport of autophagic and endosomal vesicles as a molecular interaction partner of activated CASP8 (caspase 8). The absence of FYCO1 sensitized cells to basal and TNFSF10/TRAIL-induced apoptosis by receptor accumulation and stabili ...[more]

PMID: 37418591

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