Evidence map›Paper›PMID 37418591›Full record

ArticleAutophagy2023

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

Valeria Coppola, Ilaria Marino, Uwe Warnken, Mario Falchi, Luca Pasquini, Mauro Biffoni, Ruggero De Maria, Tobias Longin Haas

Open access · hybridAbstract read
In one paragraph

Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Valeria CoppolaDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, RM, Italy.ORCID 0000-0002-5745-2572
Ilaria MarinoDepartment of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, RM, Italy.
Uwe WarnkenFunctional Proteomic Analysis, German Cancer Research Center (DKFZ), Heidelberg, BW, Germany.ORCID 0000-0001-9337-1879
Mario FalchiNational AIDS Center (CNAIDS), Rome, RM, Italy.ORCID 0000-0002-8290-5406
Luca PasquiniServizio Tecnico Scientifico Grandi Strumentazioni E Core Facilities - FAST, Rome, RM, Italy.ORCID 0000-0002-3484-6288
Mauro BiffoniDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, RM, Italy.ORCID 0000-0002-1304-9060
Ruggero De MariaDepartment of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, RM, Italy.ORCID 0000-0003-2255-0583
Tobias Longin HaasDepartment of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, RM, Italy.ORCID 0000-0003-2336-0263
Università Cattolica del Sacro Cuore · ITIstituto Superiore di Sanità · ITGerman Cancer Research Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 stabilization of the Death Inducing Signaling Complex (DISC). Loss of FYCO1 resulted in impaired transport of TNFRSF10B/TRAIL-R2/DR5 (TNF receptor superfamily member 10b) to the lysosomes in TNFSF10/TRAIL-stimulated cells. More in detail, we show that FYCO1 interacted via its C-terminal GOLD domain with the CCZ1-MON1A complex, which is necessary for RAB7A activation and for the fusion of autophagosomal/endosomal vesicles with lysosomes. We demonstrated that FYCO1 is a novel and specific CASP8 substrate. The cleavage at aspartate 1306 resulted in the release of the C-terminal GOLD domain, inactivating FYCO1 function, and allowing for the progression of apoptosis. Furthermore, the lack of FYCO1 resulted in a stronger and prolonged formation of the TNFRSF1A/TNF-R1 signaling complex. Thus, FYCO1 limits the ligand-induced and steady-state signaling of TNFR-superfamily members, providing a control mechanism that fine-tunes both apoptotic and inflammatory answers.

Indexed as

AutophagyReceptors, TNF-Related Apoptosis-Inducing LigandApoptosisCASP8 and FADD-Like Apoptosis Regulating ProteinCaspase 8Caspase 9CaspasesTNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor-alphaCASP8 and FADD-Like Apoptosis Regulating ProteinCaspase 8Caspase 9CaspasesReceptors, TNF-Related Apoptosis-Inducing LigandTNF-Related Apoptosis-Inducing LigandTumor Necrosis Factor-alphaapoptosisautophagycaspase 8FYCO1lysosomal degradationTRAIL

Identifiers

PMID37418591
PMCPMC10472876
OpenAlexW4383499496

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.