B-MYB transactivates its own promoter through SP1-binding sites

Oncogene. 1999 Feb 11;18(6):1333-9. doi: 10.1038/sj.onc.1202421.

Abstract

B-MYB is an ubiquitous protein required for mammalian cell growth. In this report we show that B-MYB transactivates its own promoter through a 120 bp segment proximal to the transcription start site. The B-MYB-responsive element does not contain myb-binding sites and gel-shift analysis shows that SP1, but not B-MYB, protein contained in SAOS2 cell extracts binds to the 120 bp B-myb promoter fragment. B-MYB-dependent transactivation is cooperatively increased in the presence of SP1, but not SP3 overexpression. When the SP1 elements of the B-myb promoter are transferred in front of a heterologous promoter, an increased response to B-MYB results. In contrast, c-MYB, the prototype member of the Myb family, is not able to activate the luciferase construct containing the SP1 elements. With the use of an SP1-GAL4 fusion protein, we have determined that the cooperative activation occurs through the domain A of SP1. These observations suggest that B-MYB functions as a coactivator of SP1, and that diverse combinations of myb and SP1 sites may dictate the responsiveness of myb-target genes to the various members of the myb family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus E1A Proteins / metabolism
  • Binding Sites
  • Cell Cycle Proteins*
  • Cell Line
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Herpes Simplex Virus Protein Vmw65 / metabolism
  • Humans
  • NF-kappa B / metabolism
  • Oligonucleotides / pharmacology
  • Promoter Regions, Genetic*
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-myb
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins*
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Sp3 Transcription Factor
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Activation* / drug effects
  • Transfection

Substances

  • Adenovirus E1A Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • GAL4 protein, S cerevisiae
  • Herpes Simplex Virus Protein Vmw65
  • MYBL2 protein, human
  • NF-kappa B
  • Oligonucleotides
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myb
  • Recombinant Fusion Proteins
  • SP3 protein, human
  • Saccharomyces cerevisiae Proteins
  • Sp1 Transcription Factor
  • Trans-Activators
  • Transcription Factors
  • Sp3 Transcription Factor