p53 suppresses c-Myb-induced trans-activation and transformation by recruiting the corepressor mSin3A.
p53 is known to repress transcription of a number of genes, but the mechanism of p53 recruitment to these target genes is unknown. The c-myb proto-oncogene product (c-Myb) positively regulates proliferation of immature hematopoietic cells, whereas p53 blocks cell cycle progression. Here, we demonstrate that p53 inhibits c-Myb-induced transcription and transformation by directly binding to c-Myb. The ability of c-Myb to maintain the undifferentiated state of M1 cells was also suppressed by p53. p53 did not affect the ability of c-Myb to bind to DNA but formed a ternary complex with the corepressor mSin3A and c-Myb. Thus, p53 antagonizes c-Myb by recruiting mSin3A to down-regulate specific Myb target genes.
Tanikawa
Jun
J
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Nomura
Teruaki
T
Macmillan
Elizabeth M
EM
Shinagawa
Toshie
T
Jin
Wanzhu
W
Kokura
Kenji
K
Baba
Daichi
D
Shirakawa
Masahiro
M
Gonda
Thomas J
TJ
Ishii
Shunsuke
S
D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism / Q000502:physiology*; D012313:RNA / Q000737:chemistry; D012097:Repressor Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
D015850:Interleukin-6; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D016159:Tumor Suppressor Protein p53; D012313:RNA; D004247:DNA; D008156:Luciferases; D005982:Glutathione Transferase; D056264:Sin3 Histone Deacetylase and Corepressor Complex