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Record W2136542008 · doi:10.1073/pnas.0900596106

Control of p53 multimerization by Ubc13 is JNK-regulated

2009· article· en· W2136542008 on OpenAlexaff
Ivan Topisirović, Gustavo J. Gutierrez, Meifan Chen, Ettore Appella, Katherine L. B. Borden, Ze’ev A. Ronai

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2009
Typearticle
Languageen
FieldMedicine
TopicCancer-related Molecular Pathways
Canadian institutionsUniversité de MontréalInstitute for Research in Immunology and Cancer
FundersNational Cancer InstituteU.S. Public Health ServiceUniversity of California, San DiegoNational Institutes of HealthLeukemia and Lymphoma Society
KeywordsPolysomePhosphorylationSuppressorRegulatorThreonineMutantUbiquitinCell biologyCytosolBiologyKinaseTranscriptional regulationUbiquitin-conjugating enzymeBiochemistryTranslation (biology)Transcription factorSerineChemistryRNARibosomeMessenger RNAUbiquitin ligaseEnzymeGene

Abstract

fetched live from OpenAlex

The p53 tumor suppressor protein is a key regulator of cellular proliferation and survival whose function is tightly regulated at the levels of transcription and protein stability. Here, we unveil the fine control of p53 on translationally active polysomes. We have previously reported that Ubc13, an E2 ubiquitin-conjugating enzyme, directly regulates p53 localization and transcriptional activity. We now demonstrate that the association of p53 and Ubc13 on polysomes requires ongoing translation and results in p53 ubiquitination that interferes with its tetramerization. JNK phosphorylation of p53 at Threonine 81 occurring on polysomes is required for the dissociation of Ubc13 from p53, leading to p53 multimerization and transcriptional activation. Inhibition of JNK activity or expression of a nonphosphorylatable mutant of p53 maintains an Ubc13-p53 complex that inhibits p53 multimerization. Our findings reveal a layer in the regulation of p53 multimerization that requires the concerted action of JNK and Ubc13 on polysome-bound p53.

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)0.001
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 score0.029
Threshold uncertainty score0.254

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.019
GPT teacher head0.289
Teacher spread0.270 · 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

Citations55
Published2009
Admission routes1
Has abstractyes

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