Effects of B-Myb on gene transcription: phosphorylation-dependent activity ans acetylation by p300.
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.
Johnson
Lance R
LR
Eppley Institute for Research in Cancer and Allied Diseases, Department of Pathology University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
Johnson
Teresa K
TK
Desler
Michelle
M
Luster
Troy A
TA
Nowling
Tamara
T
Lewis
Robert E
RE
Rizzino
Angie
A
D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D018797:Cell Cycle Proteins; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; C064352:MYBL2 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D005346:Fibroblast Growth Factors