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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1048-1055. Prepublished online as a Blood First Edition Paper on September 29, 2005; DOI 10.1182/blood-2005-06-2452. This Article Full Text (PDF) All Versions of this Article: 2005-06-2452v1 107/3/1048    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lo, J. C Articles by Fu, Y.-X. Search for Related Content PubMed PubMed Citation Articles by Lo, J. C Articles by Fu, Y.-X. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 21, 2005 Accepted September 25, 2005 Coordination between NF-B family members p50 and p52 is essential for mediating LTR signals in the development and organization of secondary lymphoid tissues James C Lo, Soumen Basak, Ethan S James, Raechel Quiambo, Marcus C Kinsella, Maria-Luisa Alegre, Falk Weih, Guido Franzoso, Alexander Hoffmann, and Yang-Xin Fu* Committee on Immunology and Department of Pathology, The University of Chicago, Chicago, IL, USA Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of Cslifornia, San Diego, La Jolla, CA, USA Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe, Karlsruhe, Germany * Corresponding author; email: yfu{at}uchicago.edu. Recent studies revealed that the LT/LTR system activates the non-canonical NF-B signaling pathway involving IKK1/IKK and NIK to direct processing of the nfb2 protein p100 to yield RelB:p52 complexes. Despite the biochemical evidence, LT, RelB, and p52-deficient mice show discrepant phenotypes. We now demonstrate that p105/p50 also constitutes an important pathway for LTR signaling. Our studies revealed that mice deficient in either p50 or p52 have defects in the formation of inguinal lymph nodes (LN), but that the complete defect in lymph node formation and splenic microarchitecture seen in LT-deficient mice is recapitulated only in mice deficient in both p50 and p52. Biochemically, we find not only that both p50- and p52-containing NF-B activities are induced by LTR signaling, but that the induction of NF-B-containing complexes by LTR engagement is perturbed in single knockouts. Importantly, the LTR can additionally activate the less well characterized p52:RelA and p50:RelB pathways, which play pivotal roles in vivo for the development and organization of lymphoid structures. Our genetic, cellular, and molecular evidence points towards a model of LT-mediated NF-B regulation in which p105/p50 and p100/p52 have distinct and coordinating molecular specificities but differ in the upstream signaling pathways that regulate them. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Basak, V. F.-S. Shih, and A. Hoffmann Generation and Activation of Multiple Dimeric Transcription Factors within the NF-{kappa}B Signaling System Mol. Cell. Biol., May 15, 2008; 28(10): 3139 - 3150. [Abstract] [Full Text] [PDF] E. Tucker, K. O'Donnell, M. Fuchsberger, A. A. Hilton, D. Metcalf, K. Greig, N. A. Sims, J. M. Quinn, W. S. Alexander, D. J. Hilton, et al. 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