| First Author | Boehm D | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 42 | Pages | 18103-8 |
| PubMed ID | 20923877 | Mgi Jnum | J:165531 |
| Mgi Id | MGI:4837607 | Doi | 10.1073/pnas.1011752107 |
| Citation | Boehm D, et al. (2010) Epstein-Barr latent membrane protein 1 transformation site 2 activates NF-kappaB in the absence of NF-kappaB essential modifier residues 133-224 or 373-419. Proc Natl Acad Sci U S A 107(42):18103-8 |
| abstractText | Epstein Barr virus latent membrane protein 1 (LMP1) induces NF-kappaB activation through transformation effector sites (TES) 1 and 2, both of which are critical for B-lymphocyte transformation. TES2 principally activates canonical NF-kappaB, which we confirm is NF-kappaB essential modifier (NEMO)-dependent and requires an intact ubiquitin binding in A20 binding inhibitor of NF-kappaB and NEMO (UBAN) domain. LMP1 TES2 activated NF-kappaB in Jurkat cell lines harboring NEMO truncated at 372 (A45) or NEMO with an in-frame deletion of 133-224 (2C), whereas TNFalpha, 12-O-Tetradecanoylphorbol-13-acetate, human T-cell leukemia virus 1 Tax, and CD40 did not. In both A45 and 2C Jurkat cell lines, LMP1 TES2-mediated NF-kappaB activation was blocked by siRNAs to TNFalpha receptor-associated factor 6 and NEMO, by IkappaB kinase inhibitors, and by the IkappaBalpha superrepressor, indicating that the NEMO mutants function to support canonical NF-kappaB activation. Expression of A45 or 2C mutants in NEMO-deficient murine embryonic fibroblasts reproduced the Jurkat phenotypes: LMP1 TES2 activated NF-kappaB in fibroblasts lacking NEMO amino acids 133-224 or 373-419, but TNFalpha and Tax did not. Further analysis indicated that TES2 did not activate NF-kappaB in cells expressing the double deletion mutant Delta133-224/Delta372-419. These data provide further evidence of the essential role for NEMO in LMP1 TES2 NF-kappaB activation and highlight the importance of unique domains within NEMO for sensing distinct NF-kappaB stimuli. |
