title: 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.
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.
authors.affiliation: Department of Biology, Boston University, Boston, MA 02215, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Garbati
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Thompson
authors.forename: Leila
authors.initials: L
authors.lastname: Haery
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Gilmore
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050881:E1A-Associated p300 Protein / Q000235:genetics* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D015321:Gene Rearrangement; D057809:HEK293 Cells; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D011485:Protein Binding; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D020569:Proto-Oncogene Proteins c-rel; D008156:Luciferases; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D051548:Histone Acetyltransferases