MSK
Search
- Page Path
- HOME > Search
Research Support, Non-U.S. Gov't
- Characterization of the rapamycin-inducible EBV LMP1 activation system
- Sang Yong Kim , Jung-Eun Kim , Jiyeon Won , Yoon-Jae Song
- J. Microbiol. 2015;53(10):732-738. Published online October 2, 2015
- DOI: https://doi.org/10.1007/s12275-015-5455-z
- 21 View
- 0 Download
- 8 Citations
-
Abstract
- Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) is required for EBV-mediated B lymphocyte transformation into proliferating lymphoblastoid cell lines (LCL). LMP1 oligomerizes spontaneously in membrane lipid rafts via its transmembrane domain and constitutively activates signal transduction pathways, including NF-κB, p38 Mitogen-Activated Protein Kinase (MAPK), and c-Jun N-terminal Kinase (JNK). Since LMP1 mimics the tumor necrosis factor receptor (TNFR), CD40, it may be effectively utilized to study the effects of constitutive activation of signal transduction pathways on cellular physiology. On the other hand, LMP1 presents a disadvantage in terms of determining the sequential events and factors involved in signaling pathways. A CD40-LMP1 chimeric molecule has been generated to overcome this limitation but does not represent the authentic and physiological nature of LMP1. In the current study, a ligand-dependent activation system for LMP1 using rapamycin-inducible dimerization was generated to delineate the LMP1 signaling pathway.
- Deletion Analysis of the Major NF-[kappa]B Activation Domain in Latent Membrane Protein 1 of Epstein-Barr Virus
- Shin Cho , Won-Keun Lee
- J. Microbiol. 1999;37(4):256-262.
- 14 View
- 0 Download
-
Abstract
- Latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) is an integral membrane protein with six transmembrane domains, which is essential for EBV-induced B cell transformation. LMP1 functions as a constitutively active tumor necrosis factor receptor (TNFR) like membrane receptor, whose signaling requires recruitment of TNFR-associated factors (TRAFs) and leads to NF-[kappa]B activation. NF-[kappa]B activation by LMP1 is critical for B cell transformation and has been linked to many phenotypic changes associated with EBV-induced B cell transformation. Deletion analysis has identified two NF-[kappa]B activation regions in the carboxy terminal cytoplasmic domains of LMP1, termed CTAR1 (residues 194-232) and CTAR2 (351-386). The membrane proximal C-terminal domain was precisely mapped to a PXQXT motif (residues 204-208) involved in TRAF binding as well as NF-[kappa]B activation. In this study, we dissected the CTAR2 region, which is the major NF-[kappa]B signaling effector of LMP1, to determine a minimal functional sequence. A series of LMP1 mutant constructs systematically deleted for the CTAR2 region were prepared, and NF-[kappa]B activation activity of these mutants were assessed by transiently expressing them in 293 cells and Jurkat T cells. The NF-[kappa]B activation domain of CTAR2 appears to reside in a stretch of 6 amino acids (residues 379-384) at the end of the carboxy terminus.
- High Prevalence of the China 1 Strain of Epstein-Barr Virus in Korea as Determined by Sequence Polymorphisms in the Carboxy-Terminal Tail of LMP1
- Sung-Gyu Cho , Won-Keun Lee
- J. Microbiol. 2003;41(2):129-136.
- 14 View
- 0 Download
-
Abstract
- The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) exhibits considerable sequence heterogeneity among EBV isolates. Seven distinct EBV strains have been defined based on sequence polymorphisms in the LMP1 gene, which are designated China 1, China 2, China 3, Alaskan, Mediterranean, NC, and the B95-8 strains. In this study, we analyzed a 30-bp deletion and sequence variations in the carboxy-terminal region of the LMP1 gene in 12 EBV isolates from spontaneous lymphoblastoid cell lines derived from individuals with non-EBV associated cancers in Korea. Eleven of the 12 isolates showed a 30-bp deletion spanning LMP1 amino acids 342 to 353, suggesting a high prevalence of the LMP1 30-bp deletion variant among EBV isolates in Korea. In addition, all 12 isolates had a 15-bp common deletion in the 33-bp repeat region and multiple base-pair changes relative to the prototype B95-8 EBV strain along with variations in the number of the 33-bp repeats. The bp changes at positions 168746, 168694, 168687, 168395, 168357, 168355, 168631, 168320, 168308, 168295, and 168225 were highly conserved among the isolates. Comparative analysis of sequence change patterns in the LMP1 carboxy-terminal coding region identified nine 30-bp deletion variants as China 1, two deletion variants as a possible interstrain between the Alaskan and China 1 strains, and a single undeleted variant as a possible variant of the Alaskan strain. These results suggest the predominance of the China 1 EBV strain in the Korean population.
First
Prev
TOP
