Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription.
We have identified a conserved region in the C-terminal domain of bromodomain-containing protein 4 (BRD4) that mediates its specific interaction with positive transcription elongation factor b (P-TEFb). This domain is highly conserved in testis-specific bromodomain protein (BRDT) and Drosophila fs(1)h. Both BRDT and fs(1)h specifically interact with P-TEFb in mammalian cells, and this interaction depends on their C-terminal domains. Overexpression of the BRD4 P-TEFb-interacting domain disrupts the interaction between the HIV transactivator Tat and P-TEFb and suppresses the ability of Tat to transactivate the HIV promoter. Incubation of cells with a synthetic peptide containing the C-terminal domain of BRD4 interferes with transactivation of the HIV promoter by the Tat protein.
Bisgrove
Dwayne A
DA
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA.
Mahmoudi
Tokameh
T
Henklein
Peter
P
Verdin
Eric
E
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D017124:Conserved Sequence; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D006678:HIV / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus; D000092468:Bromodomain Containing Proteins
D018797:Cell Cycle Proteins; D015696:Gene Products, tat; D009687:Nuclear Proteins; D042925:Positive Transcriptional Elongation Factor B; D021122:Protein Subunits; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins
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