B- myb rescues ras-induced premature senescence, which requires its transactivation domain

• Published in: Cancer letters 2001-09, Vol.171 (1), p.87-101
• Main Authors: Masselink, Hans, Vastenhouw, Nadine, Bernards, René
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; B-myb; B-Myb protein; Biological and medical sciences; BS69; Carrier Proteins - physiology; Cell Cycle Proteins; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular Senescence - physiology; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Humans; Mice; Molecular and cellular biology; N-CoR; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; Nuclear Receptor Co-Repressor 1; Protein Structure, Tertiary; Proteins - metabolism; ras Proteins - physiology; Recombinant Fusion Proteins - metabolism; Repression; Repressor Proteins - physiology; Retinoblastoma-Like Protein p107; Trans-Activators - chemistry; Trans-Activators - physiology; Transcription; Transcriptional Activation; Transfection; Transformation; Tumor Cells, Cultured; Tumor Suppressor Protein p14ARF; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(01)00631-0

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.