Evidence map›Paper›PMID 42054439›Full record

ArticleScience advances2026

PARP4 ADP-ribosylates PIDD1 to complete a phospho/SUMO/PAR-ylation cascade that orchestrates PIDDosome assembly.

Richa B Shah, Yuanyuan Li, Ashley Person, Léonie Frigon, Nina Ðukić, Ela Kini, Raymond Chen, John M Pascal, Michael S Cohen, Ivan Ahel and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Richa B ShahDepartment of Medicine, Division of Hematology and Medical Oncology, Mount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-2805-6770
Yuanyuan LiDepartment of Medicine, Division of Hematology and Medical Oncology, Mount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-1124-9421
Ashley PersonDepartment of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, USA.
Léonie FrigonDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC, Canada.ORCID 0009-0004-7020-5295
Nina ÐukićSir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID 0009-0004-6120-6421
Ela KiniDepartment of Medicine, Division of Hematology and Medical Oncology, Mount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0009-0002-0640-0497
Raymond ChenDepartment of Medicine, Division of Hematology and Medical Oncology, Mount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
John M PascalDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC, Canada.ORCID 0000-0002-2714-4317
Michael S CohenDepartment of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0002-7636-4156
Ivan AhelSir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID 0000-0002-9446-3756
John D HaleyDepartment of Pathology Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA.ORCID 0000-0002-0283-6413
Samuel SidiDepartment of Medicine, Division of Hematology and Medical Oncology, Mount Sinai Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-7649-0673

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adenosine diphosphate (ADP) ribosylation (ADPr) regulates multiple stress responses, yet substrates in the apoptotic machinery remain elusive. We show that a single, DNA damage-induced ADPr event controls proapoptotic PIDDosome (PIDD1/RAIDD/caspase-2) formation in response to unresolved interstrand DNA cross-links (ICL). ADPr targets conserved E783 in the PIDD1 death domain (DD); is catalyzed by poly(ADP-ribose) polymerase 4 (PARP4), a phylogenetically orphan PARP of previously unknown function; is reversed by the ribosylhydrolase activity of PARP14; and is triggered by Ataxia Telangiectasia and RAD3-related (ATR) phosphorylation-induced, PIAS1-mediated SUMOylation of the PIDD1 DD, which enables PARP4 docking. PIDD1 ADPr is dispensable for the recruitments of RAIDD and caspase-2 but essential for the dimerization of the caspase. Hence, denying E783 ADPr spares the onset of PIDDosome assembly but blocks its completion, thus eliminating caspase-2 activation and ensuing apoptosis. Conversely, removal of PARP14 forces apoptosis, even in cells with tolerable damage. The data identify PARP4 as an ICL response effector and illuminate a three-step modification sequence of the PIDD1 DD that conducts PIDDosome assembly from initiation to completion.

Indexed as

ADP-RibosylationCRADD Signaling Adaptor ProteinDeath Domain Receptor Signaling Adaptor ProteinsPoly(ADP-ribose) PolymerasesApoptosisCaspase 2Cysteine EndopeptidasesDNA DamageHumansPhosphorylationCASP2 protein, humanCaspase 2CRADD protein, humanCRADD Signaling Adaptor ProteinCysteine EndopeptidasesDeath Domain Receptor Signaling Adaptor ProteinsPARP14 protein, humanPIDD1 protein, humanPoly(ADP-ribose) Polymerases

Identifiers

PMID42054439
PMCPMC13127586

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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 OpenQuestion graph.