MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, enhancing the viral infection of Burkitt lymphoma cells.

MYC is an oncogenic transcription factor dysregulated in about half of total human tumors. While transcriptomic studies reveal more than 1000 genes regulated by MYC, a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocatio...

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Detalles Bibliográficos
Autores: Molina, Ester, García-Gutiérrez, Lucía, Junco, Vanessa, Perez-Olivares, Mercedes, de Yébenes, Virginia G, Blanco, Rosa, Quevedo, Laura, Acosta, Juan C, Marín, Ana V, Ulgiati, Daniela, Merino, Ramon, Delgado, M Dolores, Varela, Ignacio, Regueiro, José R, Moreno de Alborán, Ignacio, Ramiro, Almudena R, León, Javier
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/16764
Acceso en línea:http://hdl.handle.net/20.500.12105/16764
Access Level:acceso abierto
Palabra clave:Burkitt Lymphoma
Epstein-Barr Virus Infections
Animals
Humans
Mice
B-Lymphocytes
Genes, myc
Herpesvirus 4, Human
Descripción
Sumario:MYC is an oncogenic transcription factor dysregulated in about half of total human tumors. While transcriptomic studies reveal more than 1000 genes regulated by MYC, a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocations involving MYC oncogene. Most endemic BL and a fraction of sporadic BL are associated with Epstein-Barr virus (EBV) infection. The currently accepted mechanism is that EBV is the BL-causing agent inducing MYC translocation. Herein we show that the EBV receptor, CR2 (also called CD21), is a direct MYC target gene. This is based on several pieces of evidence: MYC induces CR2 expression in both proliferating and arrested cells and in the absence of protein synthesis, binds the CR2 promoter and transactivates CR2 in an E-box-dependent manner. Moreover, using mice with conditional MYC ablation we show that MYC induces CR2 in primary B cells. Importantly, modulation of MYC levels directly correlates with EBV's ability of infection in BL cells. Altogether, in contrast to the widely accepted hypothesis for the correlation between EBV and BL, we propose an alternative hypothesis in which MYC dysregulation could be the first event leading to the subsequent EBV infection.

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