Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We demonstrate that human activating transcription factor 4 (hATF4), a member of the activating transcription factor/cAMP-responsive element-binding protein (ATF/CREB) family of transcription factors, is a potent transcriptional activator in both mammalian cells and yeast. The N-terminal 113 amino acids of hATF4 activate transcription efficiently, and unexpectedly, the C-terminal bZip DNA binding domain of hATF4 also activates transcription, albeit weakly. Our results indicate that hATF4 interacts with several general transcription factors: TATA-binding protein, TFIIB, and the RAP30 subunit of TFIIF. In addition, hATF4 interacts with the coactivator CREB-binding protein (CBP) at four regions: 1) the KIX domain, 2) a region that contains the third zinc finger and the E1A-interacting domain, 3) a C-terminal region that contains the p160/SRC-1-interacting domain, and 4) the recently identified histone acetyltransferase domain. Interestingly, both the N-terminal and C-terminal regions of hATF4 interact with the above general transcription factors and CBP, providing a mechanistic explanation for their ability to activate transcription. Consistent with its role as a coactivator, CBP potentiates the ability of hATF4 to activate transcription. The potential significance of the interaction between hATF4 and multiple factors is discussed.
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PMID:Characterization of human activating transcription factor 4, a transcriptional activator that interacts with multiple domains of cAMP-responsive element-binding protein (CREB)-binding protein. 929 63

In this work, we determined how altered-function mutants affecting hydrophobic residues within the tau 1-core activation domain of the human glucocorticoid receptor (GR) influence its physical interaction with different target proteins of the transcriptional machinery. Screening of putative target proteins showed that the tau 1-core can interact with the C-terminal part of the CREB-binding protein (CBP). In addition, the previously identified interactions of the tau 1-core with the TATA-binding protein (TBP) and the Ada2 adaptor protein were localized to the C- and N-terminal regions of these proteins, respectively. A panel of mutations within the tau 1-core that either decrease or increase activation potential was used to probe the interaction of the tau 1-core domain with TBP, Ada2, and CBP. We found that the pattern of effects caused by the mutations was similar for each of the interactions and that the effects on binding generally reflected effects on gene activation potential. Thus, the predominant effect of the mutations appears to influence a property of the tau 1-core that is common to all three interactions, rather than properties that are differentially required by each of the target factor interactions, individually. Such a property could be the ability of the domain to adopt a folded conformation that is generally necessary for interaction with target factors. We have also shown that TBP, Ada2, and CBP can interact with both the tau 1-core and the GR ligand-binding domain, offering a possible mechanism for synergistic interaction between the tau 1-core and other receptor activation domains. However, other target proteins (e.g., RIP140, and SRC-1), which interact with the GR C terminus, did not show significant interactions with the tau 1-core under our conditions.
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PMID:Role of important hydrophobic amino acids in the interaction between the glucocorticoid receptor tau 1-core activation domain and target factors. 964 42

The state of chromatin (the packaging of DNA in eukaryotes) has long been recognized to have major effects on levels of gene expression, and numerous chromatin-altering strategies-including ATP-dependent remodeling and histone modification-are employed in the cell to bring about transcriptional regulation. Of these, histone acetylation is one of the best characterized, as recent years have seen the identification and further study of many histone acetyltransferase (HAT) proteins and their associated complexes. Interestingly, most of these proteins were previously shown to have coactivator or other transcription-related functions. Confirmed and putative HAT proteins have been identified from various organisms from yeast to humans, and they include Gcn5-related N-acetyltransferase (GNAT) superfamily members Gcn5, PCAF, Elp3, Hpa2, and Hat1: MYST proteins Sas2, Sas3, Esa1, MOF, Tip60, MOZ, MORF, and HBO1; global coactivators p300 and CREB-binding protein; nuclear receptor coactivators SRC-1, ACTR, and TIF2; TATA-binding protein-associated factor TAF(II)250 and its homologs; and subunits of RNA polymerase III general factor TFIIIC. The acetylation and transcriptional functions of these HATs and the native complexes containing them (such as yeast SAGA, NuA4, and possibly analogous human complexes) are discussed. In addition, some of these HATs are also known to modify certain nonhistone transcription-related proteins, including high-mobility-group chromatin proteins, activators such as p53, coactivators, and general factors. Thus, we also detail these known factor acetyltransferase (FAT) substrates and the demonstrated or potential roles of their acetylation in transcriptional processes.
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PMID:Acetylation of histones and transcription-related factors. 1083 22