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Record W2140577256 · doi:10.1096/fj.09-137695

Sumoylation of poly(ADP‐ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function

2009· article· en· W2140577256 on OpenAlexfundno aff
Simon Messner, David Schuermann, Matthias Altmeyer, Ingrid Kassner, Darja Schmidt, Primo Schär, Stefan Müller, Michael O. Rottiger

Bibliographic record

VenueThe FASEB Journal · 2009
Typearticle
Languageen
FieldMedicine
TopicPARP inhibition in cancer therapy
Canadian institutionsnot available
FundersUniversität InnsbruckUniversität ZürichTurun YliopistoUniversité LavalUniversity of DundeeDeutsche ForschungsgemeinschaftSlovenská Akadémia ViedMedizinischen Hochschule HannoverSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
KeywordsPARP1SUMO proteinCoactivatorBiologyPoly ADP ribose polymeraseAcetylationMolecular biologyTranscription factorCell biologyBiochemistryChemistryPolymeraseUbiquitinGene

Abstract

fetched live from OpenAlex

ABSTRACT Poly(ADP‐ribose) polymerase 1 (PARP1) is a chromatin‐associated nuclear protein and functions as a molecular stress sensor. At the cellular level, PARP1 has been implicated in a wide range of processes, such as maintenance of genome stability, cell death, and transcription. PARP1 functions as a transcriptional coactivator of nuclear factor KB(NF‐ΚB) and hypoxia inducible factor 1 (HIF1). In proteomic studies, PARP1 was found to be modified by small ubiquitin‐like modifiers (SUMOs). Here, we characterize PARP1 as a substrate for modification by SUMO1 and SUMO3, both in vitro and in vivo. PARP1 is sumoylated at the single lysine residue K486 within its automodification domain. Interestingly, modification of PARP1 with SUMO does not affect its ADP‐ribosylation activity but completely abrogates p300‐mediated acetylation of PARP1, revealing an intriguing crosstalk of sumoylation and acetylation on PARP1. Genetic complementation of PARP1‐depleted cells with wildtype and sumoylation‐deficient PARP1 revealed that SUMO modification of PARP1 restrains its transcriptional coactivator function and subsequently reduces gene expression of distinct PARP1‐regulated target genes. Messner, S., Schuermann, D., Altmeyer, M., Kassner, I., Schmidt, D., Schär, P., Müller, S., and Hottiger, M. O. Sumoylation of poly(ADP‐ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function. FASEB J. 23, 3978–3989 (2009). www.fasebj.org

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.201
Threshold uncertainty score0.414

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.030
GPT teacher head0.286
Teacher spread0.256 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations72
Published2009
Admission routes1
Has abstractyes

Explore more

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