Epstein–Barr virus latent membrane protein 1

Epstein–Barr virus latent membrane protein 1 (LMP1) is an Epstein–Barr virus (EBV) protein that regulates its own expression and the expression of human genes.[1] It has a molecular weight of approximately 63 kDa, and its expression induces many of the changes associated with EBV infections and activation of primary B cells.[2] LMP1 is the best-documented oncoprotein of the EBV latent gene products, as it is expressed in most EBV-related human cancers[3] such as the various malignant Epstein-Barr virus-associated lymphoproliferative diseases.[4]

The structure of LMP1 consists of a short cytoplasmic terminal tail, six trans-membrane domains, and a long cytoplasmic C-terminus, which contains three activating domains: CTARt, CTAR2, and CTAR3. Each CTAR domain contains an amino acid sequence that serves as a recognition site for cellular adaptors to bind and trigger a series of signal transduction pathways that can lead to a change in gene expression.[5]

LMP-1 is a functional homologue of tumor necrosis factor[6] and mediates signaling through the nuclear factor-κB pathway, mimicking CD40 receptor signaling.[1][3]

It is often found in the malignant Reed–Sternberg cells of Hodgkin lymphoma,[7][8] the malignant B cells of EBV-associated B cell lymphatic cancers, and the malignant NK cells of NK/T cell lymphatic cancers.[4]

References

  1. ^ a b Pratt, Z; Zhang, J; Sugden, B. (2012). "The latent membrane protein 1 (LMP1) oncogene of Epstein–Barr virus can simultaneously induce and inhibit apoptosis in B cells". Journal of Virology. 86 (8): 4380–4393. doi:10.1128/JVI.06966-11. PMC 3318665. PMID 22318153.
  2. ^ Gupta (2011). "Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines". Retrovirology. 8 (1): 39. doi:10.1186/1742-4690-8-39. PMC 3118346. PMID 21592361.
  3. ^ a b Ersing, I; Bernhardt, K; Gewurz, BE (Jun 21, 2013). "NF-κB and IRF7 pathway activation by Epstein-Barr virus Latent Membrane Protein 1". Viruses. 5 (6) (6 ed.): 1587–606. doi:10.3390/v5061587. PMC 3717723. PMID 23793113.
  4. ^ a b Rezk SA, Zhao X, Weiss LM (June 2018). "Epstein - Barr virus - associated lymphoid proliferations, a 2018 update". Human Pathology. 79: 18–41. doi:10.1016/j.humpath.2018.05.020. PMID 29885408. S2CID 47010934.
  5. ^ Li, H.; Chang, Y. (2003). "Epstein–barr virus latent membrane protein 1: Structure and functions". J. Biomed. Sci. 10 (5): 490–504. doi:10.1159/000072376. PMID 12928589. S2CID 202646382.
  6. ^ Cameron, J. E.; Yin, Q; Fewell, C; Lacey, M; McBride, J; Wang, X; Lin, Z; Schaefer, B. C.; Flemington, E. K. (2008). "Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways". Journal of Virology. 82 (4): 1946–58. doi:10.1128/JVI.02136-07. PMC 2258704. PMID 18057241.
  7. ^ Herling M, Rassidakis GZ, Medeiros LJ, et al. (June 2003). "Expression of Epstein–Barr virus latent membrane protein-1 in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma: associations with presenting features, serum interleukin 10 levels, and clinical outcome". Clin. Cancer Res. 9 (6): 2114–20. PMID 12796376.
  8. ^ Andersson J (May 2006). "Epstein–Barr virus and Hodgkin's lymphoma". Herpes. 13 (1): 12–6. PMID 16732997.