PXD033760-2

PXD033760 is an original dataset announced via ProteomeXchange.

Title	The autophagic protein FYCO1 controls TRAIL receptor induced apoptosis and is inactivated by caspase 8
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:07:27.702.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Uwe Warnken
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-08 04:07:22	ID requested
1	2023-10-24 11:18:04	announced
⏵ 2	2023-11-14 09:07:28	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:08:58	announced	2024-10-22: Updated project metadata.

Coppola V, Marino I, Warnken U, Falchi M, Pasquini L, Biffoni M, De Maria R, Haas TL, The autophagic protein FYCO1 controls TNFRSF10/TRAIL receptor induced apoptosis and is inactivated by CASP8 (caspase 8). Autophagy, 19(10):2733-2751(2023) [pubmed]

submitter keyword: apoptosis

autophagy

inflammation

death receptors

endosome maturation

lysosomal degradation

caspase 8

FYCO1

CCZ1

Uwe Warnken
contact affiliation	German Cancer Research Center (DKFZ) Clinical Cooperation Unit (CCE) Neurooncology
contact email	U.Warnken@dkfz-heidelberg.de
lab head
Uwe Warnken
contact affiliation	German Cancer Research Center Heidelberg, Clinical Cooperation Unit Neurooncology B320
contact email	u.warnken@dkfz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033760
     1. Label: PRIDE project
     2. Name: The autophagic protein FYCO1 controls TRAIL receptor induced apoptosis and is inactivated by caspase 8