A rearranged EP300 gene in the human B-cell lymphoma cell line RC-K8 encodes a disabled transcriptional co-activator that contributes to cell growth and oncogenicity

Cancer Lett. 2011 Mar 1;302(1):76-83. doi: 10.1016/j.canlet.2010.12.018. Epub 2011 Jan 12.

Abstract

Human diffuse large B-cell lymphoma cell line RC-K8 has an altered EP300 locus that encodes a C-terminally truncated histone acetyltransferase (HAT) protein (p300ΔC). We now show that p300ΔC contains 1047N-terminal amino acids of p300 fused to 25 amino acids encoded by sequences from chromosome 6. Over-expressed p300ΔC localized to nuclear subdomains and interacted with transcription factor REL. p300ΔC did not function as a co-activator for REL-directed transactivation, and blocked the ability of wild-type p300 to enhance transcriptional activation by REL. Knock down of p300ΔC in RC-K8 cells reduced their growth in both liquid culture and soft agar. Truncations of p300 were not found in eight other B-lymphoma cell lines. These results suggest that p300ΔC contributes to the oncogenic state of RC-K8 cells by acting as a defective co-activator.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation*
  • E1A-Associated p300 Protein / genetics*
  • E1A-Associated p300 Protein / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Gene Rearrangement*
  • HEK293 Cells
  • Histone Acetyltransferases / genetics*
  • Histone Acetyltransferases / metabolism
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Molecular Sequence Data
  • Protein Binding
  • Proto-Oncogene Proteins c-rel / genetics
  • Proto-Oncogene Proteins c-rel / metabolism
  • RNA Interference
  • Transcriptional Activation
  • Transfection

Substances

  • Proto-Oncogene Proteins c-rel
  • Luciferases
  • E1A-Associated p300 Protein
  • EP300 protein, human
  • Histone Acetyltransferases