title: B-myb promotes S phase and is a downstream target of the negative regulator p107 in human cells.
abstract: 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.
authors.affiliation: Thomas Jefferson University, Department of Microbiology and Immunology and Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sala
authors.forename: I
authors.initials: I
authors.lastname: Casella
authors.forename: T
authors.initials: T
authors.lastname: Bellon
authors.forename: B
authors.initials: B
authors.lastname: Calabretta
authors.forename: R J
authors.initials: RJ
authors.lastname: Watson
authors.forename: C
authors.initials: C
authors.lastname: Peschle
mesh_terms: 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
chemical_list: 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