The cooperation of B-Myb with the coactivator p300 is orchestrated by cyclins A and D1

Oncogene. 2004 Feb 19;23(7):1392-404. doi: 10.1038/sj.onc.1207255.

Abstract

B-Myb is a highly conserved member of the Myb family of transcription factors whose activity is regulated during the cell cycle. Previous work has shown that the activity of B-Myb is stimulated by cyclin A/Cdk2-dependent phosphorylation whereas interaction of B-Myb with cyclin D1 inhibits its activity. Here, we have investigated the role of p300 as a coactivator for B-Myb. We show that B-Myb-dependent transactivation is stimulated by p300 as a result of interaction between B-Myb and p300. We have mapped the sequences responsible for the interaction of B-Myb and p300 to the E1A-binding region of p300 and the transactivation domain of B-Myb, respectively. Furthermore, our data suggest that phosphorylation of B-Myb stimulates its acetylation by p300 and that the acetylation of B-Myb is necessary for the full stimulation of its transactivation potential by p300. We have also studied the effect of cyclin D1 on the cooperation of B-Myb and p300. Based on our results we propose that cyclin D1 inhibits the activity of B-Myb by interfering with the interaction of B-Myb and p300. The data reported here provide novel insight into the mechanisms by which the activity of B-Myb is regulated during the cell cycle. Taken together they suggest that the coactivator p300 plays an important role in this regulation and that the cooperation of B-Myb and p300 is orchestrated by cyclins A and D1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cell Cycle Proteins*
  • Cyclin A / metabolism*
  • Cyclin D1 / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • E1A-Associated p300 Protein
  • Mice
  • Nuclear Proteins / metabolism*
  • Sequence Deletion
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • Cell Cycle Proteins
  • Cyclin A
  • DNA-Binding Proteins
  • Mybl2 protein, mouse
  • Nuclear Proteins
  • Trans-Activators
  • Cyclin D1
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse