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Regulatory domains of the A-Myb transcription factor and its interaction with the CBP/p300 adaptor molecules
- Source :
- Scopus-Elsevier
- Publication Year :
- 1997
-
Abstract
- The A-Myb transcription factor belongs to the Myb family of oncoproteins and is likely to be involved in the regulation of proliferation and/or differentiation of normal B cells and Burkitt's lymphoma cells. To characterize in detail the domains of A-Myb that regulate its function, we have generated a series of deletion mutants and have investigated their trans-activation potential as well as their DNA-binding activity. Our results have allowed us to delineate the trans-activation domain as well as two separate regulatory regions. The boundaries of the trans-activation domain (amino acid residues 218–319) are centred on a sequence rich in charged amino acids (residues 259–281). A region (residues 320–482) localized immediately downstream of the trans-activation domain and containing a newly identified conserved stretch of 48 residues markedly inhibits specific DNA binding. Finally the last 110 residues of A-Myb (residues 643–752), which include a sequence conserved in all mammalian myb genes (region III), negatively regulate the maximal trans-activation potential of A-Myb. We have also investigated the functional interaction between A-Myb and the nuclear adaptor molecule CBP [cAMP response element-binding protein (CREB)-binding protein]. We demonstrate that CBP synergizes with A-Myb in a dose-dependent fashion, and that this co-operative effect can be inhibited by E1A and can also be observed with the CBP homologue p300. We show that this functional synergism requires the presence of the A-Myb charged sequence and that it involves physical interaction between A-Myb and the CREB-binding domain of CBP.
- Subjects :
- Cell Cycle Proteins
Plasma protein binding
P300-CBP Transcription Factors
Biology
CREB
Biochemistry
Mice
Proto-Oncogene Proteins c-myb
Acetyltransferases
Proto-Oncogene Proteins
Animals
Humans
MYB
p300-CBP Transcription Factors
Molecular Biology
Transcription factor
Gene
Histone Acetyltransferases
Sequence Deletion
fungi
Cell Biology
3T3 Cells
Molecular biology
Cell biology
DNA-Binding Proteins
Regulatory sequence
biology.protein
Trans-Activators
Research Article
Protein Binding
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Scopus-Elsevier
- Accession number :
- edsair.doi.dedup.....28d292c35a13610e0001289a29f863b7