Human T-cell leukemia virus type I tax masks c-Myc function through a cAMP-dependent pathway

J Biol Chem. 1996 Apr 19;271(16):9730-8. doi: 10.1074/jbc.271.16.9730.


Human T-cell leukemia virus type I Tax is a pleiotropic gene regulator that functions through CREB/ATF- and NF-kappaB-mediated pathways. In most contexts, Tax is a potent gene activator. Here, we describe an unexpected finding of Myc repression by Tax. In cells that overexpress human T-cell leukemia virus type I Tax, the detection of c-Myc protein in the nucleus by a monoclonal antibody was masked. Tax prevented immunological visualization of a Myc epitope contained within amino acids 45-104, resulting in interference with Myc function in transcription and in anchorage-independent cell growth. Tax did not affect steady-state protein levels since detection of c-Myc with other antibodies was unperturbed. Four observations suggest that this Tax-Myc interaction is mediated through CREB/ATF signal transduction. 1) Tax point mutants, selectively defective for activation of CREB/ATF but not NF-kappaB, failed to mask c-Myc; 2) masking of Myc was abolished when Tax-expressing cells were treated with protein kinase inhibitor H-9; 3) Tax-specific shielding of Myc is absent in cells (B1R) that are genetically defective for cAMP signaling; and 4) forskolin treatment of cells mimicked Tax in masking the Myc epitope. Considered collectively, these findings suggest a regulation of Myc function at the level of localized protein conformation.

Publication types

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

MeSH terms

  • Animals
  • Cell Division
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Cloning, Molecular
  • Cyclic AMP / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Epitopes / analysis
  • Escherichia coli
  • Gene Products, tax / metabolism*
  • Genes, myc
  • HeLa Cells
  • Human T-lymphotropic virus 1 / metabolism*
  • Humans
  • Mutagenesis
  • Plasmids
  • Protein Conformation
  • Proto-Oncogene Proteins c-myc / analysis
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Restriction Mapping
  • Sequence Deletion
  • Signal Transduction
  • Transfection


  • Cyclic AMP Response Element-Binding Protein
  • Epitopes
  • Gene Products, tax
  • Proto-Oncogene Proteins c-myc
  • Recombinant Proteins
  • Cyclic AMP
  • Chloramphenicol O-Acetyltransferase