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A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein

Polyglutamine diseases are inherited neurodegenerative diseases caused by the expanded polyglutamine proteins (polyQs). We have identified a novel guanosine triphosphatase (GTPase) named CRAG that contains a nuclear localization signal (NLS) sequence and forms nuclear inclusions in response to stres...

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Autores principales: Qin, Qingyu, Inatome, Ryoko, Hotta, Azusa, Kojima, Masaki, Yamamura, Hirohei, Hirai, Hirokazu, Yoshizawa, Toshihiro, Tanaka, Hirofumi, Fukami, Kiyoko, Yanagi, Shigeru
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063670/
https://www.ncbi.nlm.nih.gov/pubmed/16461359
http://dx.doi.org/10.1083/jcb.200505079
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author Qin, Qingyu
Inatome, Ryoko
Hotta, Azusa
Kojima, Masaki
Yamamura, Hirohei
Hirai, Hirokazu
Yoshizawa, Toshihiro
Tanaka, Hirofumi
Fukami, Kiyoko
Yanagi, Shigeru
author_facet Qin, Qingyu
Inatome, Ryoko
Hotta, Azusa
Kojima, Masaki
Yamamura, Hirohei
Hirai, Hirokazu
Yoshizawa, Toshihiro
Tanaka, Hirofumi
Fukami, Kiyoko
Yanagi, Shigeru
author_sort Qin, Qingyu
collection PubMed
description Polyglutamine diseases are inherited neurodegenerative diseases caused by the expanded polyglutamine proteins (polyQs). We have identified a novel guanosine triphosphatase (GTPase) named CRAG that contains a nuclear localization signal (NLS) sequence and forms nuclear inclusions in response to stress. After ultraviolet irradiation, CRAG interacted with and induced an enlarged ring-like structure of promyelocytic leukemia protein (PML) body in a GTPase-dependent manner. Reactive oxygen species (ROS) generated by polyQ accumulation triggered the association of CRAG with polyQ and the nuclear translocation of the CRAG–polyQ complex. Furthermore, CRAG promoted the degradation of polyQ at PML/CRAG bodies through the ubiquitin–proteasome pathway. CRAG knockdown by small interfering RNA in neuronal cells consistently blocked the nuclear translocation of polyQ and enhanced polyQ-mediated cell death. We propose that CRAG is a modulator of PML function and dynamics in ROS signaling and is protectively involved in the pathogenesis of polyglutamine diseases.
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spelling pubmed-20636702007-11-29 A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein Qin, Qingyu Inatome, Ryoko Hotta, Azusa Kojima, Masaki Yamamura, Hirohei Hirai, Hirokazu Yoshizawa, Toshihiro Tanaka, Hirofumi Fukami, Kiyoko Yanagi, Shigeru J Cell Biol Research Articles Polyglutamine diseases are inherited neurodegenerative diseases caused by the expanded polyglutamine proteins (polyQs). We have identified a novel guanosine triphosphatase (GTPase) named CRAG that contains a nuclear localization signal (NLS) sequence and forms nuclear inclusions in response to stress. After ultraviolet irradiation, CRAG interacted with and induced an enlarged ring-like structure of promyelocytic leukemia protein (PML) body in a GTPase-dependent manner. Reactive oxygen species (ROS) generated by polyQ accumulation triggered the association of CRAG with polyQ and the nuclear translocation of the CRAG–polyQ complex. Furthermore, CRAG promoted the degradation of polyQ at PML/CRAG bodies through the ubiquitin–proteasome pathway. CRAG knockdown by small interfering RNA in neuronal cells consistently blocked the nuclear translocation of polyQ and enhanced polyQ-mediated cell death. We propose that CRAG is a modulator of PML function and dynamics in ROS signaling and is protectively involved in the pathogenesis of polyglutamine diseases. The Rockefeller University Press 2006-02-13 /pmc/articles/PMC2063670/ /pubmed/16461359 http://dx.doi.org/10.1083/jcb.200505079 Text en Copyright © 2006, 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 Research Articles
Qin, Qingyu
Inatome, Ryoko
Hotta, Azusa
Kojima, Masaki
Yamamura, Hirohei
Hirai, Hirokazu
Yoshizawa, Toshihiro
Tanaka, Hirofumi
Fukami, Kiyoko
Yanagi, Shigeru
A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein
title A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein
title_full A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein
title_fullStr A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein
title_full_unstemmed A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein
title_short A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein
title_sort novel gtpase, crag, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063670/
https://www.ncbi.nlm.nih.gov/pubmed/16461359
http://dx.doi.org/10.1083/jcb.200505079
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