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Keratin attenuates tumor necrosis factor–induced cytotoxicity through association with TRADD
Keratin 8 and 18 (K8/18) are the major components of intermediate filament (IF) proteins of simple or single-layered epithelia. Recent data show that normal and malignant epithelial cells deficient in K8/18 are nearly 100 times more sensitive to tumor necrosis factor (TNF)–induced cell death. We hav...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150850/ https://www.ncbi.nlm.nih.gov/pubmed/11684708 http://dx.doi.org/10.1083/jcb.200103078 |
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author | Inada, Hiroyasu Izawa, Ichiro Nishizawa, Miwako Fujita, Eriko Kiyono, Tohru Takahashi, Toshitada Momoi, Takashi Inagaki, Masaki |
author_facet | Inada, Hiroyasu Izawa, Ichiro Nishizawa, Miwako Fujita, Eriko Kiyono, Tohru Takahashi, Toshitada Momoi, Takashi Inagaki, Masaki |
author_sort | Inada, Hiroyasu |
collection | PubMed |
description | Keratin 8 and 18 (K8/18) are the major components of intermediate filament (IF) proteins of simple or single-layered epithelia. Recent data show that normal and malignant epithelial cells deficient in K8/18 are nearly 100 times more sensitive to tumor necrosis factor (TNF)–induced cell death. We have now identified human TNF receptor type 1 (TNFR1)–associated death domain protein (TRADD) to be the K18-interacting protein. Among IF proteins tested in two-hybrid systems, TRADD specifically bound K18 and K14, type I (acidic) keratins. The COOH-terminal region of TRADD interacted with the coil Ia of the rod domain of K18. Endogenous TRADD coimmunoprecipitated with K18, and colocalized with K8/18 filaments in human mammary epithelial cells. Overexpression of the NH(2) terminus (amino acids 1–270) of K18 containing the TRADD-binding domain as well as overexpression of K8/18 in SW13 cells, which are devoid of keratins, rendered the cells more resistant to killing by TNF. We also showed that overexpressed NH(2) termini of K18 and K8/18 were associated with endogenous TRADD in SW13 cells, resulting in the inhibition of caspase-8 activation. These results indicate that K18 may sequester TRADD to attenuate interactions between TRADD and activated TNFR1 and moderate TNF-induced apoptosis in simple epithelial cells. |
format | Text |
id | pubmed-2150850 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21508502008-05-01 Keratin attenuates tumor necrosis factor–induced cytotoxicity through association with TRADD Inada, Hiroyasu Izawa, Ichiro Nishizawa, Miwako Fujita, Eriko Kiyono, Tohru Takahashi, Toshitada Momoi, Takashi Inagaki, Masaki J Cell Biol Article Keratin 8 and 18 (K8/18) are the major components of intermediate filament (IF) proteins of simple or single-layered epithelia. Recent data show that normal and malignant epithelial cells deficient in K8/18 are nearly 100 times more sensitive to tumor necrosis factor (TNF)–induced cell death. We have now identified human TNF receptor type 1 (TNFR1)–associated death domain protein (TRADD) to be the K18-interacting protein. Among IF proteins tested in two-hybrid systems, TRADD specifically bound K18 and K14, type I (acidic) keratins. The COOH-terminal region of TRADD interacted with the coil Ia of the rod domain of K18. Endogenous TRADD coimmunoprecipitated with K18, and colocalized with K8/18 filaments in human mammary epithelial cells. Overexpression of the NH(2) terminus (amino acids 1–270) of K18 containing the TRADD-binding domain as well as overexpression of K8/18 in SW13 cells, which are devoid of keratins, rendered the cells more resistant to killing by TNF. We also showed that overexpressed NH(2) termini of K18 and K8/18 were associated with endogenous TRADD in SW13 cells, resulting in the inhibition of caspase-8 activation. These results indicate that K18 may sequester TRADD to attenuate interactions between TRADD and activated TNFR1 and moderate TNF-induced apoptosis in simple epithelial cells. The Rockefeller University Press 2001-10-29 /pmc/articles/PMC2150850/ /pubmed/11684708 http://dx.doi.org/10.1083/jcb.200103078 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Inada, Hiroyasu Izawa, Ichiro Nishizawa, Miwako Fujita, Eriko Kiyono, Tohru Takahashi, Toshitada Momoi, Takashi Inagaki, Masaki Keratin attenuates tumor necrosis factor–induced cytotoxicity through association with TRADD |
title | Keratin attenuates tumor necrosis factor–induced cytotoxicity through association with TRADD |
title_full | Keratin attenuates tumor necrosis factor–induced cytotoxicity through association with TRADD |
title_fullStr | Keratin attenuates tumor necrosis factor–induced cytotoxicity through association with TRADD |
title_full_unstemmed | Keratin attenuates tumor necrosis factor–induced cytotoxicity through association with TRADD |
title_short | Keratin attenuates tumor necrosis factor–induced cytotoxicity through association with TRADD |
title_sort | keratin attenuates tumor necrosis factor–induced cytotoxicity through association with tradd |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150850/ https://www.ncbi.nlm.nih.gov/pubmed/11684708 http://dx.doi.org/10.1083/jcb.200103078 |
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