B-myb rescues ras-induced premature senescence, which requires its transactivation domain.
B-myb, a ubiquitously expressed member of the myb gene family, is highly regulated throughout the cell cycle and appears to be required for cell cycle progression. In contrast to its relatives A-myb, c-myb, and v-myb, no transforming activity of B-myb has been reported thus far. We report here that B-myb can rescue senescence induced by an activated ras oncogene in rodent cells in vitro. We show that transformation by B-Myb involves its ability to activate transcription. Similar to other oncogenic transcription factors, such as c-Myc and E2F, we show that B-Myb also has repression activity. We demonstrate that the C-terminus of B-Myb can function as a repressor of transcription, that B-Myb interacts with the repressor molecules BS69 and N-CoR and that the repression function, like the transactivation domain, contributes to B-myb transformation.
Masselink
H
H
Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Vastenhouw
N
N
Bernards
R
R
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D018797:Cell Cycle Proteins; D016922:Cellular Senescence / Q000502:physiology*; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology; D056971:Nuclear Receptor Co-Repressor 1; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D050720:Retinoblastoma-Like Protein p107; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000502:physiology*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; C539127:NCOR1 protein, human; C539128:Ncor1 protein, mouse; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011506:Proteins; C489485:Rbl1 protein, mouse; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D050720:Retinoblastoma-Like Protein p107; D015534:Trans-Activators; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; C094763:ZMYND11 protein, human; C490622:Zmynd11 protein, mouse; D018631:ras Proteins