B-myb promotes S phase and is a downstream target of the negative regulator p107 in human cells

J Biol Chem. 1996 Apr 19;271(16):9363-7. doi: 10.1074/jbc.271.16.9363.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E2 Proteins / metabolism
  • Animals
  • Bone Neoplasms
  • Cell Cycle Proteins*
  • Cell Cycle*
  • Cell Division
  • Cell Line
  • Cell Survival
  • DNA Replication
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma
  • Homeostasis
  • Humans
  • Kinetics
  • Luciferases / biosynthesis
  • Luciferases / metabolism
  • Mice
  • Nuclear Proteins / metabolism*
  • Oncogenes
  • Osteosarcoma
  • Plasmids
  • Recombinant Proteins / metabolism
  • Retinoblastoma Protein / biosynthesis
  • Retinoblastoma-Like Protein p107
  • S Phase
  • Trans-Activators*
  • Transcription Factors / biosynthesis
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Adenovirus E2 Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MYBL2 protein, human
  • Mybl2 protein, mouse
  • Nuclear Proteins
  • RBL1 protein, human
  • Rbl1 protein, mouse
  • Recombinant Proteins
  • Retinoblastoma Protein
  • Retinoblastoma-Like Protein p107
  • Trans-Activators
  • Transcription Factors
  • Luciferases