Roles of TRAF2 and TRAF3 in Epstein-Barr virus latent membrane protein 1-induced alternative NF-kappa B activation
- Authors
- Song, YJ[Song, Yoon-Jae]; Kang, MS[Kang, Myung-Soo]
- Issue Date
- Oct-2010
- Publisher
- SPRINGER
- Keywords
- Epstein-Barr virus; Latent membrane protein 1; NF-kappa B; p100 processing
- Citation
- VIRUS GENES, v.41, no.2, pp.174 - 180
- Indexed
- SCIE
SCOPUS
- Journal Title
- VIRUS GENES
- Volume
- 41
- Number
- 2
- Start Page
- 174
- End Page
- 180
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/73117
- DOI
- 10.1007/s11262-010-0505-4
- ISSN
- 0920-8569
- Abstract
- Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)-induced NF-kappa B activation is essential for EBV-transformed B cell survival. LMP1 has two C-terminal cytoplasmic domains referred to as C-Terminal Activation Regions (CTAR) 1 and 2 that activate the alternative and canonical NF-kappa B pathways, respectively. While CTAR2 activates TRAF6, IKK beta and IKK gamma-dependent canonical NF-kappa B pathway, CTAR1 interacts with TRAF2 and TRAF3 and activates NIK and IKK alpha-dependent alternative NF-kappa B pathway involving p100 processing into functional p52. Using IKK alpha(-/-), IKK beta(-/-), IKK gamma(-/-), TRAF2(-/-), TRAF3(-/-), TRAF6(-/-), and NIK(aly/aly) mouse embryonic fibroblasts (MEFs), potential roles of these proteins in LMP1-induced alternative NF-kappa B activation were investigated. Deficiency in IKK alpha or functional NIK, but not in IKK beta, IKK gamma, or TRAF6, severely impaired LMP1-induced p100 processing. Notably, p100 was constitutively processed in TRAF2(-/-) or TRAF3(-/-) MEFs independently of LMP1 suggesting that TRAF2 or TRAF3 may play a regulatory role in p100 processing. Subsequently, TRAF2 or TRAF3 over-expression in HEK293 cells significantly blocked LMP1-induced p100 processing. The LMP1 CTAR1 expression in 293HEK cells activated the alternative p65/p52 complex while CTAR2 failed to do so. Taken together, LMP1 activates alternative NF-kappa B pathway through functional NIK and IKK alpha that is regulated by TRAF2 or TRAF3.
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- Appears in
Collections - Medicine > Department of Medicine > 1. Journal Articles
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