Effects of B-Myb on gene transcription: Phosphorylation-dependent activity and acetylation by p300

Lance R. Johnson, Teresa K. Johnson, Michelle Desler, Troy A. Luster, Tamara Nowling, Robert E Lewis, A Angie Rizzino

Research output: Contribution to journalArticle

45 Scopus citations

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 languageEnglish (US)
Pages (from-to)4088-4097
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number6
DOIs
Publication statusPublished - Feb 8 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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