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)

The ability of p53 to function as a tumor suppressor is linked to its function as a transcriptional activator, since p53 mutants that do not transactivate are unable to suppress tumor cell growth. Previous studies identified an activation domain in the amino terminal 40 residues of the protein, a region that binds to several general transcription factors and to some oncogene products. For example, mdm-2, a cellular oncoprotein, binds to this region and represses p53 transactivation. Here we describe a new activation domain within the amino terminus of p53 that maps between amino acids 40-83, and whose residues trp-53 and phe-54 are critical for function both in yeast and in mammalian cells. In vivo studies in yeast show that the new activation subdomain, unlike the previously described, is mdm-2 independent. Both p53 activation subdomains (1-40 and 40-83) require the yeast adaptor complex ADA2/ADA3/GCN5 for transcriptional activation. Moreover, since activation by p53 requires GCN5's enzymatic histone acetyltransferase domain, p53 may regulate gene expression by influencing chromatin modification.
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PMID:Two tandem and independent sub-activation domains in the amino terminus of p53 require the adaptor complex for activity. 926 67

Beta-catenin is the key transcriptional activator of the Wnt pathway important for development and tissue homeostasis of multicellular organisms. Its deregulation contributes to many human cancers. The beta-catenin transcriptional activator complex continues to be defined, but already contains several proteins with chromatin remodeling activity. Here we show that two members of histone acetyltransferase complexes without enzymatic activity, hADA2a and hADA3, are required for full activity of beta-catenin. hADA2a and hADA3 physically interact with beta-catenin, and the interaction is mediated through Armadillo repeats 6 through 12 and the C-terminal transactivation domain of beta-catenin. Both hADA2a and hADA3 reside with beta-catenin at the enhancer for the Wnt target gene c-Myc. RNA interference-mediated reduction of hADA2a and hADA3 results in reduced beta-catenin acetylation, reduced activity in reporter gene assays and reduced activation of endogenous beta-catenin target genes. Overall, loss of hADA2a and hADA3 negatively impacts beta-catenin-mediated proliferation. Our studies identify hADA2a and hADA3 as crucial cofactors of beta-catenin that are likely involved in the assembly of transactivation-competent beta-catenin complexes at Wnt target genes.
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PMID:hADA2a and hADA3 are required for acetylation, transcriptional activity and proliferative effects of beta-catenin. 1834 24