{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:32:39Z","timestamp":1790638359788,"version":"4.1.0"},"reference-count":26,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5511","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2001,3,16]]},"abstract":"<jats:p>\n            The role of NF-\u03baB\u2013inducing kinase (NIK) in cytokine signaling remains controversial. To identify the physiologic functions of NIK, we disrupted the NIK locus by gene targeting. Although NIK\n            <jats:sup>\u2013\/\u2013<\/jats:sup>\n            mice displayed abnormalities in both lymphoid tissue development and antibody responses, NIK\n            <jats:sup>\u2013\/\u2013<\/jats:sup>\n            cells manifested normal NF-\u03baB DNA binding activity when treated with a variety of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and lymphotoxin-\u03b2 (LT\u03b2). However, NIK was selectively required for gene transcription induced through ligation of LT\u03b2 receptor but not TNF receptors. These results reveal that NIK regulates the transcriptional activity of NF-\u03baB in a receptor-restricted manner.\n          <\/jats:p>","DOI":"10.1126\/science.1058453","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:47:44Z","timestamp":1027763264000},"page":"2162-2165","source":"Crossref","is-referenced-by-count":338,"title":["Defective Lymphotoxin-\u03b2 Receptor-Induced NF-\u03baB Transcriptional Activity in NIK-Deficient Mice"],"prefix":"10.1126","volume":"291","author":[{"given":"Li","family":"Yin","sequence":"first","affiliation":[{"name":"Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wu","sequence":"additional","affiliation":[{"name":"Tularik Inc., 2 Corporate Drive, South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Wesche","sequence":"additional","affiliation":[{"name":"Tularik Inc., 2 Corporate Drive, South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cora D.","family":"Arthur","sequence":"additional","affiliation":[{"name":"Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Michael","family":"White","sequence":"additional","affiliation":[{"name":"Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David V.","family":"Goeddel","sequence":"additional","affiliation":[{"name":"Tularik Inc., 2 Corporate Drive, South San Francisco, CA 94080, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.225"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","unstructured":"C. H. Regnier et al. Cell 90 373 (1997).","DOI":"10.1016\/S0092-8674(00)80344-X"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/41493"},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","unstructured":"F. Mercurio et al. Science 278 860 (1997).","DOI":"10.1126\/science.278.5339.860"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5339.866"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80406-7"},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","unstructured":"S. Yamaoka et al. Cell 93 1231 (1998).","DOI":"10.1016\/S0092-8674(00)81466-X"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/26261"},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","first-page":"27339","DOI":"10.1074\/jbc.274.39.27339","volume":"274","author":"Karin M.","year":"1999","unstructured":"Karin M., J. Biol. Chem. 274, 27339 (1999).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/385540a0"},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","first-page":"9792","DOI":"10.1073\/pnas.94.18.9792","volume":"94","author":"Song H. Y.","year":"1997","unstructured":"Song H. Y., Regnier C. H., Kirschning C. J., Goeddel D. V., Rothe M., Proc. Natl. Acad. Sci. U.S.A. 94, 9792 (1997).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","unstructured":"S. Miyawaki et al. Eur. J. Immunol. 24 429 (1994).","DOI":"10.1002\/eji.1830240224"},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","unstructured":"R. Shinkura et al. Nature Genet. 22 74 (1999).","DOI":"10.1038\/8780"},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","unstructured":"N. Garceau et al. J. Exp. Med. 191 381 (2000).","DOI":"10.1084\/jem.191.2.381"},{"key":"e_1_3_1_16_2","doi-asserted-by":"crossref","unstructured":"S. Fagarasan et al. J. Exp. Med. 191 1477 (2000).","DOI":"10.1084\/jem.191.9.1477"},{"key":"e_1_3_1_17_2","unstructured":"The NIK gene was targeted in GS-1 embryonic stem cells by replacing 1.3 kb of DNA containing the first 120 base pairs of exon 1 with a neomycin resistance gene (18). NIK \u2212\/\u2212 mice were maintained on either 129\/SvEv or 129\/SvEv \u00d7 C57BL\/6 backgrounds. NIK \u2212\/\u2212 mice were more susceptible to bacterial eye infections but showed no gross abnormalities in growth behavior or capacities to reproduce or nurse."},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80588-9"},{"key":"e_1_3_1_19_2","unstructured":"See Science Online (www.sciencemag.org\/cgi\/content\/full\/291\/5511\/2162\/DC1)."},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","unstructured":"K. P. Hoeflich et al. Nature 406 86 (2000).","DOI":"10.1038\/35017574"},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","unstructured":"M. Bonnard et al. EMBO J. 19 4976 (2000).","DOI":"10.1093\/emboj\/19.18.4976"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.10.5258"},{"key":"e_1_3_1_23_2","doi-asserted-by":"crossref","unstructured":"M. Tanaka et al. Immunity 10 421 (1999).","DOI":"10.1016\/S1074-7613(00)80042-4"},{"key":"e_1_3_1_24_2","doi-asserted-by":"crossref","unstructured":"M. A. Meraz et al. Cell 84 431 (1996).","DOI":"10.1016\/S0092-8674(00)81288-X"},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","unstructured":"J. L. Browning et al. J. Immunol. 159 3288 (1997).","DOI":"10.4049\/jimmunol.159.7.3288"},{"key":"e_1_3_1_26_2","first-page":"5349","volume":"14","author":"Liou H. C.","year":"1994","unstructured":"Liou H. C., Sha W. C., Scott M. L., Baltimore D., Mol. Cell. Biol. 14, 5349 (1994).","journal-title":"Mol. Cell. Biol."},{"key":"e_1_3_1_27_2","unstructured":"We thank J. Browning for LT\u03b2R mAb; D. Novack S. Teitelbaun and Y. Choi for osteoprotegerin ligand; and W. Sha for the (NF-\u03baB) 2 -Luc reporter construct. Supported by grants from NIH and Tularik Inc. L.Y. is a Postdoctoral Fellow of the Cancer Research Institute."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1058453","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:57:11Z","timestamp":1704841031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1058453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,3,16]]},"references-count":26,"journal-issue":{"issue":"5511","published-print":{"date-parts":[[2001,3,16]]}},"alternative-id":["10.1126\/science.1058453"],"URL":"https:\/\/doi.org\/10.1126\/science.1058453","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,3,16]]}}}