RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100 - PubMed (original) (raw)

. 2003 Jun 27;278(26):23278-84.

doi: 10.1074/jbc.M300106200. Epub 2003 Apr 21.

Affiliations

• PMID: 12709443
• DOI: 10.1074/jbc.M300106200

Free article

RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100

Emmanuel Derudder et al. J Biol Chem. 2003.

Free article

Abstract

Tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin-beta receptor (LTbetaR) signaling both play important roles in inflammatory and immune responses through activation of NF-kappaB. Using various deficient mouse embryonic fibroblast cells, we have compared the signaling pathways leading to NF-kappaB induction in response to TNF-alpha and LTbetaR activation. We demonstrate that LTbetaR ligation induces not only RelA/p50 dimers but also RelB/p50 dimers, whereas TNF-alpha induces only RelA/p50 dimers. LTbetaR-induced binding of RelB/p50 requires processing of p100 that is mediated by IKKalpha but is independent of IKKbeta, NEMO/IKKgamma, and RelA. Moreover, we show that RelB, p50, and p100 can associate in the same complex and that TNF-alpha but not LTbeta signaling increases the association of p100 with RelB/p50 dimers in the nucleus, leading to the specific inhibition of RelB DNA binding. These results suggest that the alternative NF-kappaB pathway based on p100 processing may account not only for the activation of RelB/p52 dimers but also for that of RelB/p50 dimers and that p100 regulates the binding activity of RelB/p50 dimers via at least two distinct mechanisms depending on the signaling pathway involved.

PubMed Disclaimer

Similar articles

• Lymphotoxin beta receptor induces sequential activation of distinct NF-kappa B factors via separate signaling pathways.
  Müller JR, Siebenlist U. Müller JR, et al. J Biol Chem. 2003 Apr 4;278(14):12006-12. doi: 10.1074/jbc.M210768200. Epub 2003 Jan 28. J Biol Chem. 2003. PMID: 12556537
• Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers.
  Bonizzi G, Bebien M, Otero DC, Johnson-Vroom KE, Cao Y, Vu D, Jegga AG, Aronow BJ, Ghosh G, Rickert RC, Karin M. Bonizzi G, et al. EMBO J. 2004 Oct 27;23(21):4202-10. doi: 10.1038/sj.emboj.7600391. Epub 2004 Oct 7. EMBO J. 2004. PMID: 15470505 Free PMC article.
• RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF.
  Yilmaz ZB, Weih DS, Sivakumar V, Weih F. Yilmaz ZB, et al. EMBO J. 2003 Jan 2;22(1):121-30. doi: 10.1093/emboj/cdg004. EMBO J. 2003. PMID: 12505990 Free PMC article.
• Regulation and function of IKK and IKK-related kinases.
  Häcker H, Karin M. Häcker H, et al. Sci STKE. 2006 Oct 17;2006(357):re13. doi: 10.1126/stke.3572006re13. Sci STKE. 2006. PMID: 17047224 Review.
• Non-canonical NF-κB signaling pathway.
  Sun SC. Sun SC. Cell Res. 2011 Jan;21(1):71-85. doi: 10.1038/cr.2010.177. Epub 2010 Dec 21. Cell Res. 2011. PMID: 21173796 Free PMC article. Review.

Cited by

• Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB.
  Huang WC, Ju TK, Hung MC, Chen CC. Huang WC, et al. Mol Cell. 2007 Apr 13;26(1):75-87. doi: 10.1016/j.molcel.2007.02.019. Mol Cell. 2007. PMID: 17434128 Free PMC article.
• A20-binding inhibitor of nuclear factor-kappaB (NF-kappaB)-2 (ABIN-2) is an activator of inhibitor of NF-kappaB (IkappaB) kinase alpha (IKKalpha)-mediated NF-kappaB transcriptional activity.
  Leotoing L, Chereau F, Baron S, Hube F, Valencia HJ, Bordereaux D, Demmers JA, Strouboulis J, Baud V. Leotoing L, et al. J Biol Chem. 2011 Sep 16;286(37):32277-88. doi: 10.1074/jbc.M111.236448. Epub 2011 Jul 22. J Biol Chem. 2011. PMID: 21784860 Free PMC article.
• A TNF-p100 pathway subverts noncanonical NF-κB signaling in inflamed secondary lymphoid organs.
  Mukherjee T, Chatterjee B, Dhar A, Bais SS, Chawla M, Roy P, George A, Bal V, Rath S, Basak S. Mukherjee T, et al. EMBO J. 2017 Dec 1;36(23):3501-3516. doi: 10.15252/embj.201796919. Epub 2017 Oct 23. EMBO J. 2017. PMID: 29061763 Free PMC article.
• Roles of NF-κB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches.
  Park MH, Hong JT. Park MH, et al. Cells. 2016 Mar 29;5(2):15. doi: 10.3390/cells5020015. Cells. 2016. PMID: 27043634 Free PMC article. Review.
• p100 Deficiency is insufficient for full activation of the alternative NF-κB pathway: TNF cooperates with p52-RelB in target gene transcription.
  Lovas A, Weidemann A, Albrecht D, Wiechert L, Weih D, Weih F. Lovas A, et al. PLoS One. 2012;7(8):e42741. doi: 10.1371/journal.pone.0042741. Epub 2012 Aug 6. PLoS One. 2012. PMID: 22880094 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • GlyGen glycoinformatics resource
  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal