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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...

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Autores principales: Inada, Hiroyasu, Izawa, Ichiro, Nishizawa, Miwako, Fujita, Eriko, Kiyono, Tohru, Takahashi, Toshitada, Momoi, Takashi, Inagaki, Masaki
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
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.
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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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