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.

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.