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Record W7000657314

Function and regulation of histone deacetylase 4

2006· dissertation· en· W7000657314 on OpenAlexafffund

Bibliographic record

VenueeScholarship@McGill (McGill) · 2006
Typedissertation
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHistone Deacetylase Inhibitors Research
Canadian institutionsMcGill UniversityLibrary and Archives Canada
FundersNational Cancer InstituteCanadian Institutes of Health ResearchMcGill University
KeywordsHDAC4HDAC10SAP30Histone deacetylase 5Subcellular localizationNuclear export signalHistone deacetylase 2HistoneHistone AcetyltransferasesHistone deacetylase
DOInot available

Abstract

fetched live from OpenAlex

Histone acetyltransferases and histone deacetylases (HDACs) maintain dynamic acetylation and deacetylation of histories and other proteins in vivo, and are actively involved in the control of gene transcription and other nuclear processes. One mechanism by which functions of these enzymes are regulated operates through differential intracellular compartmentalization. HDAC4, -5, -7 and -9, the four members of class IIa, shuttle between the nucleus and the cytoplasm in a manner dependent on specific phosphorylation stimulated by several known kinases, and these deacetylases possess intrinsic nuclear import and export signals for dynamic nucleocytoplasmic trafficking. The ability to change their intracellular localization implies that class IIa HDACs have some potential functions in different subcellular compartments. To gain additional insights into this, I first focused on studying the function and regulation of HDAC4. As a result, I identified protein kinase D3 as a novel kinase for HDAC4 and found that this kinase physically interacts with HDAC4 and stimulates its nuclear export. Then I tried to purify protein complexes of RFXANK and ANKRA2, two homologous ankyrin-repeat proteins that are known to associate with HDCA4, using the tandem affinity purification (TAP) strategy. The results that I have obtained reveal a novel mechanism for regulating the nuclear export of HDAC4 and suggest that its cytoplasmic localization may also be indicative of potential cytoplasmic functions rather than just for simple sequestration from its nuclear targets.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.004
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

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 communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.001

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 head0.009
GPT teacher head0.268
Teacher spread0.259 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2006
Admission routes2
Has abstractyes

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