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

Ester Molina, Lucía García-Gutiérrez, Vanessa Junco, Mercedes Perez-Olivares, Virginia G. de Yébenes, Rosa Blanco, Laura Quevedo, Juan C. Acosta, Ana V. Marín, Daniela Ulgiati, Ramon Merino, M. Dolores Delgado, Ignacio Varela, José R. Regueiro, Ignacio Moreno de Alborán, Almudena R. Ramiro, Javier León

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3358-3370
Number of pages13
JournalOncogene
Volume42
Issue number45
DOIs
Publication statusPublished - 3 Nov 2023

Fingerprint

Dive into the research topics of 'MYC directly transactivates CR2/CD21, the receptor of the Epstein–Barr virus, enhancing the viral infection of Burkitt lymphoma cells'. Together they form a unique fingerprint.

Cite this