Abstract
Polycomb group (PcG) proteins are chromatin modifiers that are necessary for the maintenance and renewal of embryonic and adult stem cells. However, overexpression of the PcG protein, Bmi-1, causes lymphoma in transgenic mice. We show that Bmi-1 is up-regulated in Hodgkin lymphoma (HL) cells by the Epstein-Barr virus (EBV) oncogene latent membrane protein-1 (LMP1) and that this up-regulation is mediated by NF-kappaB signaling. We also show that Bmi-1 is up-regulated by NF-kappaB in EBV-negative HL cells. Down-regulation of LMP1 and Bmi-1 decreased the survival of HL cells, suggesting that Bmi-1 may mediate the prosurvival effects of LMP1-induced NF-kappaB signaling in HL cells. Transcriptional targets of Bmi-1 were identified after its knockdown in an HL cell line. We show here that Bmi-1 and LMP1 down-regulate the ataxia telangiectasia-mutated (ATM) tumor suppressor and conclude that Bmi-1 contributes to LMP1-induced oncogenesis in HL.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Line
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Cell Survival
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Down-Regulation
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic*
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Herpesvirus 4, Human / metabolism*
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Hodgkin Disease / genetics
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Hodgkin Disease / metabolism*
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Hodgkin Disease / pathology
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Humans
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NF-kappa B / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Polycomb Repressive Complex 1
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
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Up-Regulation
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / metabolism*
Substances
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BMI1 protein, human
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Cell Cycle Proteins
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DNA-Binding Proteins
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EBV-associated membrane antigen, Epstein-Barr virus
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NF-kappa B
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Nuclear Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Tumor Suppressor Proteins
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Viral Matrix Proteins
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Polycomb Repressive Complex 1
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Atm protein, mouse
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Protein Serine-Threonine Kinases