Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histone deacetylase 3 (HDAC3) is one of four members of the human class I histone deacetylases that are implicated in transcriptional repression through deacetylation of acetyllysines in amino-terminal tails of core histones. In an immunoaffinity purification using anti-HDAC3, transcription factor TFII-I copurified with HDAC3. Specificity of the HDAC3-TFII-I interaction was confirmed by coimmunoprecipitation of epitope-tagged proteins, GST pull-down assays, and protein colocalization with indirect immunofluorescence. An anti-TFII-I immunoprecipitate contained histone deacetylase enzymatic activity. Mutational analyses revealed that the carboxyl-terminal of HDAC3 (residues 373-401) and residues 363-606 of TFII-I were required for the HDAC3-TFII-I interaction. Transcriptional activation by TFII-I was severely reduced by overexpression of HDAC3. These results suggest that HDAC3 modulates some of the functions of TFII-I and provides a link between histone deacetylase and a multifunctional transcriptional activator.
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PMID:Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I. 1239 87

The multifunctional transcription factor TFII-I is tyrosine phosphorylated in response to extracellular growth signals and transcriptionally activates growth-promoting genes. However, whether activation of TFII-I also directly affects the cell cycle profile is unknown. Here we show that under normal growth conditions, TFII-I is recruited to the cyclin D1 promoter and transcriptionally activates this gene. Most strikingly, upon cell cycle arrest resulting from genotoxic stress and p53 activation, TFII-I is ubiquitinated and targeted for proteasomal degradation in a p53- and ATM (ataxia telangiectasia mutated)-dependent manner. Consistent with a direct role of TFII-I in cell cycle regulation and cellular proliferation, stable and ectopic expression of wild-type TFII-I increases cyclin D1 levels, resulting in accelerated entry to and exit from S phase, and overcomes p53-mediated cell cycle arrest, despite radiation. We further show that the transcriptional regulation of cyclin D1 and cell cycle control by TFII-I are dependent on its tyrosine phosphorylation at positions 248 and 611, sites required for its growth signal-mediated transcriptional activity. Taken together, our data define TFII-I as a growth signal-dependent transcriptional activator that is critical for cell cycle control and proliferation and further reveal that genotoxic stress-induced degradation of TFII-I results in cell cycle arrest.
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PMID:Inhibition of TFII-I-dependent cell cycle regulation by p53. 1631 17

Src is a nonreceptor protein tyrosine kinase that is expressed widely throughout the central nervous system and is involved in diverse biological functions. Mice homozygous for a spontaneous mutation in Src (Src (thl/thl) ) exhibited hypersociability and hyperactivity along with impairments in visuospatial, amygdala-dependent, and motor learning as well as an increased startle response to loud tones. The phenotype of Src (thl/thl) mice showed significant overlap with Williams-Beuren syndrome (WBS), a disorder caused by the deletion of several genes, including General Transcription Factor 2-I (GTF2I). Src phosphorylation regulates the movement of GTF2I protein (TFII-I) between the nucleus, where it is a transcriptional activator, and the cytoplasm, where it regulates trafficking of transient receptor potential cation channel, subfamily C, member 3 (TRPC3) subunits to the plasma membrane. Here, we demonstrate altered cellular localization of both TFII-I and TRPC3 in the Src mutants, suggesting that disruption of Src can phenocopy behavioral phenotypes observed in WBS through its regulation of TFII-I.
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PMID:Disruption of Src Is Associated with Phenotypes Related to Williams-Beuren Syndrome and Altered Cellular Localization of TFII-I 2646 74