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Record W2039485415 · doi:10.1016/j.febslet.2004.12.073

p53 is a NF‐Y‐ and p21‐independent, Sp1‐dependent repressor of cyclin B1 transcription

2005· article· en· W2039485415 on OpenAlexaff
Steven A. Innocente, Jonathan M. Lee

Bibliographic record

VenueFEBS Letters · 2005
Typearticle
Languageen
FieldMedicine
TopicCancer-related Molecular Pathways
Canadian institutionsMcMaster UniversityUniversity of OttawaHamilton Regional Laboratory Medicine Program
Fundersnot available
KeywordsCyclin ACyclin A2Cyclin DCyclin BMolecular biologyBiologyG2-M DNA damage checkpointCyclin B1Cyclin-dependent kinase complexCyclin ECyclinCell biologyRepressorTranscription factorCancer researchCell cycle checkpointCell cycleGeneticsCyclin-dependent kinase 1Gene

Abstract

fetched live from OpenAlex

The p53 tumour suppressor protein is a DNA-binding transcription factor activated in response to DNA damage. Inactivation of the p53 gene occurs in 40-60% of human tumours and a substantial body of work indicates that loss of p53 activity is a critical step in oncogenesis. p53 helps to protect against neoplasia by inducing death in cells that have sustained irreparable DNA damage or by blocking cell cycle progression to allow time for DNA repair. We have previously reported that p53 prevents G2/M transition by decreasing intracellular levels of cyclin B1 protein and attenuating the activity of the cyclin B1 promoter [S.A. Innocente, J.L. Abrahamson, J.P. Cogswell, J.M. Lee, p53 regulates a G2 checkpoint through cyclin B1, Proc. Natl. Acad. Sci. USA 96 (1999) 2147-2152]. The ability of p53 to control mitotic initiation by regulating intracellular cyclin B1 levels suggests that a cyclin B1-dependent G2 checkpoint has a role in preventing neoplastic transformation. Here, we show that p53-mediated attenuation of the cyclin B1 promoter occurs in both p21+/+ and p21-/- cell lines. Furthermore, promoter attenuation is dependent on the presence of functional Sp1 binding sites and is independent of the NF-Y binding sites. We also find that wild-type, but not mutant, p53 protein binds Sp1 and the cyclin B1 promoter. This suggests that wild-type p53 mediates transcriptional repression of cyclin B1 through the Sp1 transcription factor.

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 score0.064
Threshold uncertainty score0.776

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 head0.013
GPT teacher head0.246
Teacher spread0.233 · 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

Citations90
Published2005
Admission routes1
Has abstractyes

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