Abstract
The c-Myb transcription factor is a proto-oncoprotein whose latent transforming activity can be unmasked by truncation of either terminus. Because both ends of Myb are involved in negative regulation, we tested whether they could associate in a two-hybrid assay and identified a carboxy-terminal motif that interacts with the amino-terminal DNA-binding domain. The EVES motif is highly conserved in vertebrate c-Myb proteins and contains a known site of phosphorylation previously implicated in the negative regulation of c-Myb. Interestingly, a related EVES motif is present in p100, a ubiquitously expressed transcriptional coactivator found in diverse species. We show that p100 interacts with and influences the activity of c-Myb, implicating it in the regulation of c-Myb, differentiation, and cell growth. Our results suggest that Myb is regulated by a novel mechanism in which intramolecular interactions and conformational changes control the intermolecular associations among Myb, p100, and the transcriptional apparatus.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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Binding, Competitive
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Conserved Sequence
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Endonucleases
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Gene Expression Regulation, Neoplastic
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Homeostasis
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Humans
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Molecular Sequence Data
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Phosphorylation
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-myb
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Trans-Activators / chemistry
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Trans-Activators / genetics*
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Trans-Activators / metabolism*
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Transcription Factors / chemistry
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Transcription Factors / metabolism
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Transcription, Genetic
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Yeasts / genetics
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Yeasts / metabolism
Substances
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DNA-Binding Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-myb
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Recombinant Proteins
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Trans-Activators
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Transcription Factors
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Endonucleases
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SND1 protein, human
Associated data
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GENBANK/L22741
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GENBANK/M12848
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GENBANK/M14129
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GENBANK/M15024
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GENBANK/U22055
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GENBANK/U40029