The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways.

[en] The lymphotoxin-beta receptor (LTbetaR) plays critical roles in inflammation and lymphoid organogenesis through activation of NF-kappaB. In addition to activation of the classical NF-kappaB, ligation of this receptor induces the processing of the cytosolic NF-kappaB2/p100 precursor to yield the mature p52 subunit, followed by translocation of p52 to the nucleus. This activation of NF-kappaB2 requires NIK and IKKalpha, while NEMO/IKKgamma is dispensable for p100 processing. IKKbeta-dependent activation of canonical NF-kappaB is required for the expression but not processing of p100 and for the expression of proinflammatory molecules including VCAM-1, MIP-1beta, and MIP-2 in response to LTbetaR ligation. In contrast, IKKalpha controls the induction by LTbetaR ligation of chemokines and cytokines involved in lymphoid organogenesis, including SLC, BLC, ELC, SDF1, and BAFF.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Dejardin, Emmanuel ; Université de Liège - ULiège > GIGA-R : Virologie - Immunologie

Droin, Nathalie

Delhase, Mireille

Haas, Elvira

Cao, Yixue

Makris, Constantin

Li, Zhi-Wei

Karin, Michael

Ware, Carl

Green, Douglas

Language :

English

Title :

The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways.

Publication date :

October 2002

Journal title :

Immunity

ISSN :

1074-7613

eISSN :

1097-4180

Publisher :

Cell Press, Cambridge, United States - Massachusetts

Volume :

Pages :

525-535

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 14 November 2011

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Bibliography

Alcamo E., Mizgerd J.P., Horwitz B.H., Bronson R., Beg A.A., Scott M., Doerschuk C.M., Hynes R.O., Baltimore D. Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment. J. Immunol. 167:2001;1592-1600.
Alcamo E., Hacohen N., Schulte L.C., Rennert P.D., Hynes R.O., Baltimore D. Requirement for the NF-kappaB family member RelA in the development of secondary lymphoid organs. J. Exp. Med. 195:2002;233-244.
Alimzhanov M.B., Kuprash D.V., Kosco-Vilbois M.H., Luz A., Turetskaya R.L., Tarakhovsky A., Rajewsky K., Nedospasov S.A., Pfeffer K. Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient mice. Proc. Natl. Acad. Sci. USA. 94:1997;9302-9307.
Ansel K.M., Cyster J.G. Chemokines in lymphopoiesis and lymphoid organ development. Curr. Opin. Immunol. 13:2001;172-179.
Banks T.A., Rouse B.T., Kerley M.K., Blair P.J., Godfrey V.L., Kuklin N.A., Bouley D.M., Thomas J., Kanangat S., Mucenski M.L. Lymphotoxin-alpha-deficient mice. Effects on secondary lymphoid organ development and humoral immune responsiveness. J. Immunol. 155:1995;1685-1693.
Barkett M., Gilmore T.D. Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene. 18:1999;6910-6924.
Batten M., Groom J., Cachero T.G., Qian F., Schneider P., Tschopp J., Browning J.L., Mackay F. BAFF mediates survival of peripheral immature B lymphocytes. J. Exp. Med. 192:2000;1453-1466.
Browning J.L., French L.E. Visualization of lymphotoxin-beta and lymphotoxin-beta receptor expression in mouse embryos. J. Immunol. 168:2002;5079-5087.
Browning J.L., Dougas I., Ngam-ek A., Bourdon P.R., Ehrenfels B.N., Miatkowski K., Zafari M., Yampaglia A.M., Lawton P., Meier W.et al. Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors. J. Immunol. 154:1995;33-46.
Burkly L., Hession C., Ogata L., Reilly C., Marconi L.A., Olson D., Tizard R., Cate R., Lo D. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature. 373:1995;531-536.
Caamano J.H., Rizzo C.A., Durham S.K., Barton D.S., Raventos-Suarez C., Snapper C.M., Bravo R. Nuclear factor (NF)-kappa B2 (p100/p52) is required for normal splenic microarchitecture and B cell-mediated immune responses. J. Exp. Med. 187:1998;185-196.
Cao Y., Bonizzi G., Seagroves T.N., Greten F.R., Johnson R., Schmidt E.V., Karin M. IKKα provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell. 107:2001;763-775.
De Togni P., Goellner J., Ruddle N.H., Streeter P.R., Fick A., Mariathasan S., Smith S.C., Carlson R., Shornick L.P., Strauss-Schoenberger J.et al. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 264:1994;703-707.
Dejardin E., Bonizzi G., Bellahcene A., Castronovo V., Merville M.P., Bours V. Highly-expressed p100/p52 (NFKB2) sequesters other NF-kappa B-related proteins in the cytoplasm of human breast cancer cells. Oncogene. 11:1995;1835-1841.
Dejardin E., Deregowski V., Greimers R., Cai Z., Chouaib S., Merville M.P., Bours V. Regulation of major histocompatibility complex class I expression by NF-kappaB-related proteins in breast cancer cells. Oncogene. 16:1998;3299-3307.
Dejardin E., Deregowski V., Chapelier M., Jacobs N., Gielen J., Merville M.P., Bours V. Regulation of NF-kappaB activity by I kappaB-related proteins in adenocarcinoma cells. Oncogene. 18:1999;2567-2577.
Delhase M., Hayakawa M., Chen Y., Karin M. Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science. 284:1999;309-313.
DiDonato J.A., Hayakawa M., Rothwarf D.M., Zandi E., Karin M. A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature. 388:1997;548-554.
Dobrzanski P., Ryseck R.P., Bravo R. Specific inhibition of RelB/p52 transcriptional activity by the C-terminal domain of p100. Oncogene. 10:1995;1003-1007.
Egawa T., Kawabata K., Kawamoto H., Amada K., Okamoto R., Fujii N., Kishimoto T., Katsura Y., Nagasawa T. The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor. Immunity. 15:2001;323-334.
Force W.R., Walter B.N., Hession C., Tizard R., Kozak C.A., Browning J.L., Ware C.F. Mouse lymphotoxin-beta receptor. Molecular genetics, ligand binding, and expression. J. Immunol. 155:1995;5280-5288.
Force W.R., Glass A.A., Benedict C.A., Cheung T.C., Lama J., Ware C.F. Discrete signaling regions in the lymphotoxin-beta receptor for tumor necrosis factor receptor-associated factor binding, subcellular localization, and activation of cell death and NF-kappaB pathways. J. Biol. Chem. 275:2000;11121-11129.
Forster R., Schubel A., Breitfeld D., Kremmer E., Renner-Muller I., Wolf E., Lipp M. CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell. 99:1999;23-33.
Franzoso G., Carlson L., Poljak L., Shores E.W., Epstein S., Leonardi A., Grinberg A., Tran T., Scharton-Kersten T., Anver M.et al. Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture. J. Exp. Med. 187:1998;147-159.
Fu Y.X., Chaplin D.D. Development and maturation of secondary lymphoid tissues. Annu. Rev. Immunol. 17:1999;399-433.
Futterer A., Mink K., Luz A., Kosco-Vilbois M.H., Pfeffer K. The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity. 9:1998;59-70.
Gunn M.D., Kyuwa S., Tam C., Kakiuchi T., Matsuzawa A., Williams L.T., Nakano H. Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization. J. Exp. Med. 189:1999;451-460.
Hu Y., Baud V., Delhase M., Zhang P., Deerinck T., Ellisman M., Johnson R., Karin M. Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinase. Science. 284:1999;316-320.
Hu Y., Baud V., Oga T., Kim K.I., Yoshida K., Karin M. IKKalpha controls formation of the epidermis independently of NF-kappaB. Nature. 410:2001;710-714.
Kaisho T., Takeda K., Tsujimura T., Kawai T., Nomura F., Terada N., Akira S. IkappaB kinase alpha is essential for mature B cell development and function. J. Exp. Med. 193:2001;417-426.
Karin M., Ben-Neriah Y. Phosphorylation meets ubiquitination. the control of NF-[kappa]B activity Annu. Rev. Immunol. 18:2000;621-663.
Koni P.A., Sacca R., Lawton P., Browning J.L., Ruddle N.H., Flavell R.A. Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity. 6:1997;491-500.
Li Q., Lu Q., Hwang J.Y., Buscher D., Lee K.F., Izpisua-Belmonte J.C., Verma I.M. IKK1-deficient mice exhibit abnormal development of skin and skeleton. Genes Dev. 13:1999;1322-1328. a.
Li Q., Van Antwerp D., Mercurio F., Lee K.F., Verma I.M. Severe liver degeneration in mice lacking the IkappaB kinase 2 gene. Science. 284:1999;321-325. b.
Li Z.W., Chu W., Hu Y., Delhase M., Deerinck T., Ellisman M., Johnson R., Karin M. The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis. J. Exp. Med. 189:1999;1839-1845. c.
Li Q., Estepa G., Memet S., Israel A., Verma I.M. Complete lack of NF-kappaB activity in IKK1 and IKK2 double-deficient mice. additional defect in neurulation Genes Dev. 14:2000;1729-1733.
Liptay S., Schmid R.M., Nabel E.G., Nabel G.J. Transcriptional regulation of NF-kappa B2. evidence for kappa B-mediated positive and negative autoregulation Mol. Cell. Biol. 14:1994;7695-7703.
Locksley R.M., Killeen N., Lenardo M.J. The TNF and TNF receptor superfamilies. integrating mammalian biology Cell. 104:2001;487-501.
Luther S.A., Tang H.L., Hyman P.L., Farr A.G., Cyster J.G. Coexpression of the chemokines ELC and SLC by T zone stromal cells and deletion of the ELC gene in the plt/plt mouse. Proc. Natl. Acad. Sci. USA. 97:2000;12694-12699.
Makris C., Godfrey V.L., Krahn-Senftleben G., Takahashi T., Roberts J.L., Schwarz T., Feng L., Johnson R.S., Karin M. Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti. Mol. Cell. 5:2000;969-979.
Matsumoto M., Iwamasa K., Rennert P.D., Yamada T., Suzuki R., Matsushima A., Okabe M., Fujita S., Yokoyama M. Involvement of distinct cellular compartments in the abnormal lymphoid organogenesis in lymphotoxin-alpha-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis. J. Immunol. 163:1999;1584-1591.
Matsushima A., Kaisho T., Rennert P.D., Nakano H., Kurosawa K., Uchida D., Takeda K., Akira S., Matsumoto M. Essential role of nuclear factor (NF)-kappaB-inducing kinase and inhibitor of kappaB (IkappaB) kinase alpha in NF-kappaB activation through lymphotoxin beta receptor, but not through tumor necrosis factor receptor I. J. Exp. Med. 193:2001;631-636.
May M.J., D'Acquisto F., Madge L.A., Glockner J., Pober J.S., Ghosh S. Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex. Science. 289:2000;1550-1554.
Moore P.A., Belvedere O., Orr A., Pieri K., LaFleur D.W., Feng P., Soppet D., Charters M., Gentz R., Parmelee D.et al. Blys. member of the tumor necrosis factor family and b lymphocyte stimulator Science. 285:1999;260-263.
Neumann B., Luz A., Pfeffer K., Holzmann B. Defective Peyer's patch organogenesis in mice lacking the 55-kD receptor for tumor necrosis factor. J. Exp. Med. 184:1996;259-264.
Ngo V.N., Korner H., Gunn M.D., Schmidt K.N., Riminton D.S., Cooper M.D., Browning J.L., Sedgwick J.D., Cyster J.G. Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J. Exp. Med. 189:1999;403-412.
Ngo V.N., Cornall R.J., Cyster J.G. Splenic T zone development is B cell dependent. J. Exp. Med. 194:2001;1649-1660.
Pepin N., Roulston A., Lacoste J., Lin R., Hiscott J. Subcellular redistribution of HTLV-1 Tax protein by NF-kappa B/Rel transcription factors. Virology. 204:1994;706-716.
Regnier C.H., Song H.Y., Gao X., Goeddel D.V., Cao Z., Rothe M. Identification and characterization of an IkappaB kinase. Cell. 90:1997;373-383.
Reif K., Ekland E.H., Ohl L., Nakano H., Lipp M., Forster R., Cyster J.G. Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position. Nature. 416:2002;94-99.
Rothwarf, D.M., and Karin, M. (1999). The NF-kappa B activation pathway: a paradigm in information transfer from membrane to nucleus. Sci STKE 1999, RE1.
Rothwarf D.M., Zandi E., Natoli G., Karin M. IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature. 395:1998;297-300.
Rudolph D., Yeh W.C., Wakeham A., Rudolph B., Nallainathan D., Potter J., Elia A.J., Mak T.W. Severe liver degeneration and lack of NF-kappaB activation in NEMO/IKKgamma-deficient mice. Genes Dev. 14:2000;854-862.
Schiemann B., Gommerman J.L., Vora K., Cachero T.G., Shulga-Morskaya S., Dobles M., Frew E., Scott M.L. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science. 293:2001;2111-2114.
Senftleben U., Cao Y., Xiao G., Greten F.R., Krahn G., Bonizzi G., Chen Y., Hu Y., Fong A., Sun S.C., Karin M. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science. 293:2001;1495-1499.
Sha W.C., Liou H.-C., Tuomanen E.I., Baltimore D. Targeted disruption of the p50 subunit of NF-B leads to multifocal defects in immune responses. Cell. 80:1995;321-330.
Shakhov A.N., Nedospasov S.A. Expression profiling in knockout mice. lymphotoxin versus tumor necrosis factor in the maintenance of splenic microarchitecture Cytokine Growth Factor Rev. 12:2001;107-119.
Shinkura R., Kitada K., Matsuda F., Tashiro K., Ikuta K., Suzuki M., Kogishi K., Serikawa T., Honjo T. Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase. Nat. Genet. 22:1999;74-77.
Shu H.B., Agranoff A.B., Nabel E.G., Leung K., Duckett C.S., Neish A.S., Collins T., Nabel G.J. Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells. Mol. Cell. Biol. 13:1993;6283-6289.
Siebenlist U., Franzoso G., Brown K. Structure, regulation and function of NF-kappa B. Annu. Rev. Cell Biol. 10:1994;405-455.
Silverman N., Maniatis T. NF-kappaB signaling pathways in mammalian and insect innate immunity. Genes Dev. 15:2001;2321-2342.
Solan N.J., Miyoshi H., Carmona E.M., Brean G.D., Paya C.V. RelB cellular regulation and transcriptional activity are regulated by p100. J. Biol. Chem. 277:2002;1405-1418.
Takeda K., Takeuchi O., Tsujimura T., Itami S., Adachi O., Kawai T., Sanjo H., Yoshikawa K., Terada N., Akira S. Limb and skin abnormalities in mice lacking IKKalpha. Science. 284:1999;313-316.
Tanaka M., Fuentes M.E., Yamaguchi K., Durnin M.H., Dalrymple S.A., Hardy K.L., Goeddel D.V. Embryonic lethality, liver degeneration, and impaired NF-kappa B activation in IKK-beta-deficient mice. Immunity. 10:1999;421-429.
VanArsdale T.L., Ware C.F. TNF receptor signal transduction. Ligand-dependent stimulation of a serine protein kinase activity associated with (CD120a) TNFR60. J. Immunol. 153:1994;3043-3050.
Vassileva G., Soto H., Zlotnik A., Nakano H., Kakiuchi T., Hedrick J.A., Lira S.A. The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes. J. Exp. Med. 190:1999;1183-1188.
Weih D.S., Yilmaz Z.B., Weih F. Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines. J. Immunol. 167:2001;1909-1919.
Weih F., Carrasco D., Durham S.K., Barton D.S., Rizzo C.A., Ryseck R.P., Lira S.A., Bravo R. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell. 80:1995;331-340.
Weih F., Durham S.K., Barton D.S., Sha W.C., Baltimore D., Bravo R. Both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent. J. Immunol. 157:1996;3974-3979.
Woronicz J.D., Gao X., Cao Z., Rothe M., Goeddel D.V. IkappaB kinase-beta. NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK Science. 278:1997;866-869.
Xiao G., Harhaj E.W., Sun S.C. NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol. Cell. 7:2001;401-409.
Yamaoka S., Courtois G., Bessia C., Whiteside S.T., Weil R., Agou F., Kirk H.E., Kay R.J., Israel A. Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation. Cell. 93:1998;1231-1240.
Yin L., Wu L., Wesche H., Arthur C.D., White J.M., Goeddel D.V., Schreiber R.D. Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Science. 291:2001;2162-2165.
Zandi E., Rothwarf D.M., Delhase M., Hayakawa M., Karin M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell. 91:1997;243-252.