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Beschreibung

Latent membrane protein 2 (UniProt: P13285, also known as Terminal protein) is encoded by the LMP2 gene (Gene ID: 3783751) in Epstein-Barr virus. EBV is a gamma-herpesvirus, a causative agent of infectious mononucleosis. In healthy individuals, EBV typically establishes a persistent latent infection in which the virus can be detected in resting, nonproliferating peripheral B-lymphocytes. These latently infected cells express only 2 virally encoded genes, LMP2A and EBNA1. Although the majority of virus infected individuals remain healthy, EBV has been implicated in the pathogenesis of African Burkitt s lymphoma and nasopharyngeal carcinoma. LMP2A, a multi-pass membrane protein, localizes in plasma membrane lipid rafts. It maintains EBV latent infection of B cells by preventing lytic reactivation of the virus in response to surface immunoglobulin (sIg) cross-linking. It acts like a dominant negative inhibitor of the sIg-associated protein tyrosine kinases, LYN and SYK. It is also reported to block the translocation of the B-cell antigen receptor (BCR) into lipid rafts, which prevents the subsequent signaling and accelerated internalization of the BCR upon BCR cross-linking. It also serves as a molecular scaffold to recruit SYK, LYN and E3 protein-ubiquitin ligases leading to ubiquitination and degradation of these tyrosine kinases. LMP2A also exhibits a constitutive signaling activity in non-transformed cells, inducing bypass of normal B lymphocyte developmental checkpoints, which allows immunoglobulin-negative cells to colonize peripheral lymphoid organs. (Ref.: Lai, J., et al. (2017). Sci. Rep. 7, 9923, Rancan, C., et al. (2015). PLoS Pathol. 11(6), e1004906).