Abstract
The transcription factor B-Myb is a cell-cycle regulated phosphoprotein involved in cell cycle progression through the transcriptional regulation of many genes. In this study, we show that the promoter of the fibroblast growth factor-4 (FGF-4) gene is strongly activated by B-Myb in HeLa cells and it can serve as a novel diagnostic tool for assessing B-Myb activity. Specifically, B-Myb deletion mutants were examined and domains of B-Myb required for activation of the FGF-4 promoter were identified. Using phosphorylation-deficient mutant forms of B-Myb, we also show that phosphorylation is essential for B-Myb activity. Moreover, a mutant form of B-Myb, which lacks all identified phosphorylation sites and which has little activity, can function as a dominant-negative and suppress wild-type B-Myb activity. Acetylation is another post-translational modification known to affect the activity of other Myb family members. We show that B-Myb is acetylated by the co-activator p300. We also show that the bromo and histone acetyltransferase domains of p300 are sufficient to interact with and acetylate B-Myb. These data indicate that phosphorylation of B-Myb is an essential modification for activity and that acetylation of B-Myb may play a role in B-Myb activity.
Original language | English (US) |
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Pages (from-to) | 4088-4097 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 277 |
Issue number | 6 |
DOIs | |
State | Published - Feb 8 2002 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology