Identification of human proteins functionally conserved with the yeast putative adaptors ADA2 and GCN5
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| Published in: | Molecular and Cellular Biology Vol. 16; no. 2; pp. 593 - 602 |
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Transcriptional adaptor proteins are required for full function of higher eukaryotic acidic activators in the yeast Saccharomyces cerevisiae, suggesting that this pathway of activation is evolutionarily conserved. Consistent with this view, we have identified possible human homologs of yeast ADA2 (yADA2) and yeast GCN5 (yGCN5), components of a putative adaptor complex. While there is overall sequence similarity between the yeast and human proteins, perhaps more significant is conservation of key sequence features with other known adaptors. We show several functional similarities between the human and yeast adaptors. First, as shown for yADA2 and yGCN5, human ADA2 (hADA2) and human GCN5 (hGCN5) interacted in vivo in a yeast two-hybrid assay. Moreover, hGCN5 interacted with yADA2 in this assay, suggesting that the human proteins form similar complexes. Second, both yADA2 and hADA2 contain cryptic activation domains. Third, hGCN5 and yGCN5 had similar stabilizing effects on yADA2 in vivo. Furthermore, the region of yADA2 that interacted with yGCN5 mapped to the amino terminus of yADA2, which is highly conserved in hADA2. Most striking, is the behavior of the human proteins in human cells. First, GAL4-hADA2 activated transcription in HeLa cells, and second, either hADA2 or hGCN5 augmented GAL4-VP16 activation. These data indicated that the human proteins correspond to functional homologs of the yeast adaptors, suggesting that these cofactors play a key role in transcriptional activation. Transcriptional adaptor proteins are required for full function of higher eukaryotic acidic activators in the yeast Saccharomyces cerevisiae, suggesting that this pathway of activation is evolutionarily conserved. Consistent with this view, we have identified possible human homologs of yeast ADA2 (yADA2) and yeast GCN5 (yGCN5), components of a putative adaptor complex. While there is overall sequence similarity between the yeast and human proteins, perhaps more significant is conservation of key sequence features with other known adaptors. We show several functional similarities between the human and yeast adaptors. First, as shown for yADA2 and yGCN5, human ADA2 (hADA2) and human GCN5 (hGCN5) interacted in vivo in a yeast two-hybrid assay. Moreover, hGCN5 interacted with yADA2 in this assay, suggesting that the human proteins form similar complexes. Second, both yADA2 and hADA2 contain cryptic activation domains. Third, hGCN5 and yGCN5 had similar stabilizing effects on yADA2 in vivo. Furthermore, the region of yADA2 that interacted with yGCN5 mapped to the amino terminus of yADA2, which is highly conserved in hADA2. Most striking is the behavior of the human proteins in human cells. First, GAL4-hADA2 activated transcription in HeLa cells, and second, either hADA2 or hGCN5 augmented GAL4-VP16 activation. These data indicate that the human proteins correspond to functional homologs of the yeast adaptors, suggesting that these cofactors play a key role in transcriptional activation. |
| Author | R Candau N Barlev S L Berger C A Rosen P A Moore L Wang C Y Ying |
| AuthorAffiliation | Wistar Institute, Philadelphia, Pennsylvania 19104, USA |
| AuthorAffiliation_xml | – name: Wistar Institute, Philadelphia, Pennsylvania 19104, USA |
| Author_xml | – sequence: 1 givenname: Reyes surname: Candau fullname: Candau, Reyes organization: Wistar Institute – sequence: 2 givenname: Paul A. surname: Moore fullname: Moore, Paul A. organization: Human Genome Sciences Inc – sequence: 3 givenname: Lian surname: Wang fullname: Wang, Lian organization: Wistar Institute – sequence: 4 givenname: Nickolai surname: Barlev fullname: Barlev, Nickolai organization: Wistar Institute – sequence: 5 givenname: Carol Y. surname: Ying fullname: Ying, Carol Y. organization: Wistar Institute – sequence: 6 givenname: Craig A. surname: Rosen fullname: Rosen, Craig A. organization: Human Genome Sciences Inc – sequence: 7 givenname: Shelley L. surname: Berger fullname: Berger, Shelley L. email: berger@wista.wistar.upenn.edu organization: Wistar Institute |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/8552087$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright © 1996, American Society for Microbiology 1996 |
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Mendeley... Transcriptional adaptor proteins are required for full function of higher eukaryotic acidic activators in the yeast Saccharomyces cerevisiae, suggesting that... |
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| SubjectTerms | Adaptor Proteins, Signal Transducing Amino Acid Sequence Bacterial Proteins - metabolism Cell Cycle Proteins Conserved Sequence DNA, Complementary - genetics DNA-Binding Proteins Fungal Proteins - genetics Fungal Proteins - metabolism Gene Expression Regulation HeLa Cells Histone Acetyltransferases Humans Molecular Sequence Data p300-CBP Transcription Factors Protein Binding Protein Kinases - genetics Protein Kinases - metabolism Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae Proteins Sequence Homology, Amino Acid Serine Endopeptidases Trans-Activators - genetics Trans-Activators - metabolism Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic |
| Title | Identification of human proteins functionally conserved with the yeast putative adaptors ADA2 and GCN5 |
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