B-myb promotes S phase and is a downstream target of the negative regulator p107 in human cells.
The retinoblastoma protein family has been implicated in growth control and modulation of the activity of genes involved in cell proliferation, such as B-myb. Recent evidence indicates that the product of the B-myb gene is necessary for the growth and survival of several human and murine cell lines. Upon overexpression, B-myb induces deregulated cell growth of certain cell lines. Here we show that B-myb overexpression is able to induce DNA synthesis in p107 growth-arrested human osteosarcoma cells (SAOS2). p107 might exert its growth-suppressive activity by regulating B-myb gene transcription. Indeed, p107 down-modulated B-myb promoter activity and drastically decreased E2F-mediated transactivation. Finally, B-myb was able to stimulate DNA synthesis of both stably and transiently transfected human glioblastoma cells (T98G). Altogether, these data provide definitive evidence that the human B-myb protein is involved in growth control of human cells, and that p107 has a significant role in regulating B-myb gene activity.
Sala
A
A
Thomas Jefferson University, Department of Microbiology and Immunology and Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107, USA.
Casella
I
I
Bellon
T
T
Calabretta
B
B
Watson
R J
RJ
Peschle
C
C
D017502:Adenovirus E2 Proteins / Q000378:metabolism; D000818:Animals; D001859:Bone Neoplasms; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D009857:Oncogenes; D012516:Osteosarcoma; D010957:Plasmids; D011994:Recombinant Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D050720:Retinoblastoma-Like Protein p107; D016196:S Phase; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D017502:Adenovirus E2 Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; D009687:Nuclear Proteins; C493844:RBL1 protein, human; C489485:Rbl1 protein, mouse; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D015534:Trans-Activators; D014157:Transcription Factors; D008156:Luciferases