{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:58:06Z","timestamp":1791241086533,"version":"4.1.0"},"reference-count":35,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,4,3]]},"abstract":"<jats:p>Tumor necrosis factor (TNF) is a cytokine produced by macrophages and T lymphocytes that acts through two distinct receptors, TNFR1 (60 kD, CD120a) and TNFR2 (80 kD, CD120b), to affect cellular proliferation, differentiation, survival, and cell death. In addition to its proinflammatory actions in mucosal tissue, TNF is important for liver regeneration. Keratin 8 (K8) and keratin 18 (K18) form intermediate filaments characteristic of liver and other single cell layered, internal epithelia and their derivative cancers. K8-deficient (K8\u2212) mice, which escape embryonic lethality, develop inflammatory colorectal hyperplasia, mild liver abnormalities, and tolerate hepatectomy poorly. We show that normal and malignant epithelial cells deficient in K8 and K18 are \u223c100 times more sensitive to TNF-induced death. K8 and K18 both bind the cytoplasmic domain of TNFR2 and moderate TNF-induced, Jun NH2-terminal kinase (JNK) intracellular signaling and NF\u03baB activation. Furthermore, K8\u2212 and K18\u2212 mice are much more sensitive to TNF dependent, apoptotic liver damage induced by the injection of concanavalin A. This moderation of the effects of TNF may be the fundamental function of K8 and K18 common to liver regeneration, inflammatory bowel disease, hepatotoxin sensitivity, and the diagnostic, persistent expression of these keratins in many carcinomas.<\/jats:p>","DOI":"10.1083\/jcb.149.1.17","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:45:41Z","timestamp":1027701941000},"page":"17-22","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":236,"title":["Keratin-Dependent, Epithelial Resistance to Tumor Necrosis Factor-Induced Apoptosis"],"prefix":"10.1083","volume":"149","author":[{"given":"Carlos","family":"Caulin","sequence":"first","affiliation":[{"name":"aCancer Research Center, The Burnham Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl F.","family":"Ware","sequence":"additional","affiliation":[{"name":"bLa Jolla Institute for Allergy and Immunology, San Diego, California 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Magin","sequence":"additional","affiliation":[{"name":"cInstitut fuer Genetik, Abteilung Molekulargenetik, Universitaet Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Oshima","sequence":"additional","affiliation":[{"name":"aCancer Research Center, The Burnham Institute, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,4,3]]},"reference":[{"key":"2023072902101617700_Akermanetal1992","first-page":"G579","article-title":"Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy","volume":"263","author":"Akerman","year":"1992","journal-title":"Am. 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