BS69, an adenovirus E1A-associated protein, inhibits the transcriptional activity of c-Myb.
The carboxyl terminus of c-Myb contains a negative regulatory domain that is absent in the v-Myb oncoprotein, but conserved among all the known Myb proteins of animals. This domain inhibits transcriptional activation by c-Myb in animal cells, but not in budding yeast, suggesting that additional protein(s) present in animal cells but not yeast are required for this negative regulatory function. A yeast two-hybrid screen identified BS69, an adenovirus E1A-associated protein, as interacting with the carboxy-terminal region of c-Myb. BS69 contains regions of similarity to the PHD finger, the bromodomain, and the MYND domain, all of which are found in other proteins present in high molecular weight complexes that regulate transcription and/or modify chromatin structure. Further study showed that BS69 inhibited the transcriptional activity of c-Myb, that this inhibition was specific, that it mapped to the carboxyl termini of the two proteins and that it was dose-dependent. A direct interaction between these two proteins was observed in vitro. Furthermore, the 289R E1A protein could inhibit the BS69-mediated decrease in transcriptional activation by c-Myb. By analogy with the inhibition of the Rb/E2F regulatory axis by E1A, we propose that a BS69/Myb regulatory circuit may also be a target of disruption during oncogenesis. Oncogene (2001) 20, 125 - 132.
Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California, CA 94305-5324, USA.
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Ladendorff
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Wu
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Lipsick
D017500:Adenovirus E1A Proteins / Q000378:metabolism* / Q000502:physiology; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins; D002460:Cell Line; D056970:Co-Repressor Proteins; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011784:Quail; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D015534:Trans-Activators; C094763:ZMYND11 protein, human