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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

Overview
Journal Cancer Lett
Specialty Oncology
Date 2011 Jan 15
PMID 21232847
Citations 9
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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.

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References
1.
Muraoka M, Konishi M, Tanaka K, Shitara N, Chong J, Iwama T . p300 gene alterations in colorectal and gastric carcinomas. Oncogene. 1996; 12(7):1565-9. View

2.
Emmerich F, Meiser M, Hummel M, Demel G, Foss H, Jundt F . Overexpression of I kappa B alpha without inhibition of NF-kappaB activity and mutations in the I kappa B alpha gene in Reed-Sternberg cells. Blood. 1999; 94(9):3129-34. View

3.
Bryan E, Jokubaitis V, Chamberlain N, Baxter S, Dawson E, Choong D . Mutation analysis of EP300 in colon, breast and ovarian carcinomas. Int J Cancer. 2002; 102(2):137-41. DOI: 10.1002/ijc.10682. View

4.
Starczynowski D, Reynolds J, Gilmore T . Deletion of either C-terminal transactivation subdomain enhances the in vitro transforming activity of human transcription factor REL in chicken spleen cells. Oncogene. 2003; 22(44):6928-36. DOI: 10.1038/sj.onc.1206801. View

5.
Kalaitzidis D, Davis R, Rosenwald A, Staudt L, Gilmore T . The human B-cell lymphoma cell line RC-K8 has multiple genetic alterations that dysregulate the Rel/NF-kappaB signal transduction pathway. Oncogene. 2002; 21(57):8759-68. DOI: 10.1038/sj.onc.1206033. View