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The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and proteostasis.

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The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and proteostasis. / Kuhlbrodt, Kirsten; Janiesch, Philipp Christoph; Kevei, Éva; Segref, Alexandra; Barikbin, Roja; Hoppe, Thorsten.

in: NAT CELL BIOL, Jahrgang 13, Nr. 3, 3, 2011, S. 273-281.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kuhlbrodt, K, Janiesch, PC, Kevei, É, Segref, A, Barikbin, R & Hoppe, T 2011, 'The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and proteostasis.', NAT CELL BIOL, Jg. 13, Nr. 3, 3, S. 273-281. <http://www.ncbi.nlm.nih.gov/pubmed/21317884?dopt=Citation>

APA

Kuhlbrodt, K., Janiesch, P. C., Kevei, É., Segref, A., Barikbin, R., & Hoppe, T. (2011). The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and proteostasis. NAT CELL BIOL, 13(3), 273-281. [3]. http://www.ncbi.nlm.nih.gov/pubmed/21317884?dopt=Citation

Vancouver

Kuhlbrodt K, Janiesch PC, Kevei É, Segref A, Barikbin R, Hoppe T. The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and proteostasis. NAT CELL BIOL. 2011;13(3):273-281. 3.

Bibtex

@article{228d1700a1c2466dbafe73b00b6e1d38,
title = "The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and proteostasis.",
abstract = "Protein ubiquitylation is a key post-translational control mechanism contributing to different physiological processes, such as signal transduction and ageing. The size and linkage of a ubiquitin chain, which determines whether a substrate is efficiently targeted for proteasomal degradation, is determined by the interplay between ubiquitylation and deubiquitylation. A conserved factor that orchestrates distinct substrate-processing co-regulators in diverse species is the ubiquitin-selective chaperone CDC-48 (also known as p97). Several deubiquitylation enzymes (DUBs) have been shown to interact with CDC-48/p97, but the mechanistic and physiological relevance of these interactions remained elusive. Here we report a synergistic cooperation between CDC-48 and ATX-3 (the Caenorhabditis elegans orthologue of ataxin-3) in ubiquitin-mediated proteolysis and ageing regulation. Surprisingly, worms deficient for both cdc-48.1 and atx-3 demonstrated extended lifespan by up to 50%, mediated through the insulin-insulin-like growth factor 1 (IGF-1) signalling pathway. As lifespan extension specifically depends on the deubiquitylation activity of ATX-3, our findings identify a mechanistic link between protein degradation and longevity through editing of the ubiquitylation status of substrates involved in insulin-IGF-1 signalling.",
keywords = "Animals, Humans, Time Factors, Models, Biological, Mutation, Two-Hybrid System Techniques, Signal Transduction, Adenosine Triphosphatases/metabolism, Caenorhabditis elegans, Caenorhabditis elegans Proteins/*metabolism, Cell Cycle Proteins/metabolism, Endoplasmic Reticulum/metabolism, *Gene Expression Regulation, Insulin/metabolism, Longevity, Machado-Joseph Disease/*metabolism, Nerve Tissue Proteins/*metabolism, Ubiquitin/metabolism, Animals, Humans, Time Factors, Models, Biological, Mutation, Two-Hybrid System Techniques, Signal Transduction, Adenosine Triphosphatases/metabolism, Caenorhabditis elegans, Caenorhabditis elegans Proteins/*metabolism, Cell Cycle Proteins/metabolism, Endoplasmic Reticulum/metabolism, *Gene Expression Regulation, Insulin/metabolism, Longevity, Machado-Joseph Disease/*metabolism, Nerve Tissue Proteins/*metabolism, Ubiquitin/metabolism",
author = "Kirsten Kuhlbrodt and Janiesch, {Philipp Christoph} and {\'E}va Kevei and Alexandra Segref and Roja Barikbin and Thorsten Hoppe",
year = "2011",
language = "English",
volume = "13",
pages = "273--281",
journal = "NAT CELL BIOL",
issn = "1465-7392",
publisher = "NATURE PUBLISHING GROUP",
number = "3",

}

RIS

TY - JOUR

T1 - The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and proteostasis.

AU - Kuhlbrodt, Kirsten

AU - Janiesch, Philipp Christoph

AU - Kevei, Éva

AU - Segref, Alexandra

AU - Barikbin, Roja

AU - Hoppe, Thorsten

PY - 2011

Y1 - 2011

N2 - Protein ubiquitylation is a key post-translational control mechanism contributing to different physiological processes, such as signal transduction and ageing. The size and linkage of a ubiquitin chain, which determines whether a substrate is efficiently targeted for proteasomal degradation, is determined by the interplay between ubiquitylation and deubiquitylation. A conserved factor that orchestrates distinct substrate-processing co-regulators in diverse species is the ubiquitin-selective chaperone CDC-48 (also known as p97). Several deubiquitylation enzymes (DUBs) have been shown to interact with CDC-48/p97, but the mechanistic and physiological relevance of these interactions remained elusive. Here we report a synergistic cooperation between CDC-48 and ATX-3 (the Caenorhabditis elegans orthologue of ataxin-3) in ubiquitin-mediated proteolysis and ageing regulation. Surprisingly, worms deficient for both cdc-48.1 and atx-3 demonstrated extended lifespan by up to 50%, mediated through the insulin-insulin-like growth factor 1 (IGF-1) signalling pathway. As lifespan extension specifically depends on the deubiquitylation activity of ATX-3, our findings identify a mechanistic link between protein degradation and longevity through editing of the ubiquitylation status of substrates involved in insulin-IGF-1 signalling.

AB - Protein ubiquitylation is a key post-translational control mechanism contributing to different physiological processes, such as signal transduction and ageing. The size and linkage of a ubiquitin chain, which determines whether a substrate is efficiently targeted for proteasomal degradation, is determined by the interplay between ubiquitylation and deubiquitylation. A conserved factor that orchestrates distinct substrate-processing co-regulators in diverse species is the ubiquitin-selective chaperone CDC-48 (also known as p97). Several deubiquitylation enzymes (DUBs) have been shown to interact with CDC-48/p97, but the mechanistic and physiological relevance of these interactions remained elusive. Here we report a synergistic cooperation between CDC-48 and ATX-3 (the Caenorhabditis elegans orthologue of ataxin-3) in ubiquitin-mediated proteolysis and ageing regulation. Surprisingly, worms deficient for both cdc-48.1 and atx-3 demonstrated extended lifespan by up to 50%, mediated through the insulin-insulin-like growth factor 1 (IGF-1) signalling pathway. As lifespan extension specifically depends on the deubiquitylation activity of ATX-3, our findings identify a mechanistic link between protein degradation and longevity through editing of the ubiquitylation status of substrates involved in insulin-IGF-1 signalling.

KW - Animals

KW - Humans

KW - Time Factors

KW - Models, Biological

KW - Mutation

KW - Two-Hybrid System Techniques

KW - Signal Transduction

KW - Adenosine Triphosphatases/metabolism

KW - Caenorhabditis elegans

KW - Caenorhabditis elegans Proteins/metabolism

KW - Cell Cycle Proteins/metabolism

KW - Endoplasmic Reticulum/metabolism

KW - Gene Expression Regulation

KW - Insulin/metabolism

KW - Longevity

KW - Machado-Joseph Disease/metabolism

KW - Nerve Tissue Proteins/metabolism

KW - Ubiquitin/metabolism

KW - Animals

KW - Humans

KW - Time Factors

KW - Models, Biological

KW - Mutation

KW - Two-Hybrid System Techniques

KW - Signal Transduction

KW - Adenosine Triphosphatases/metabolism

KW - Caenorhabditis elegans

KW - Caenorhabditis elegans Proteins/metabolism

KW - Cell Cycle Proteins/metabolism

KW - Endoplasmic Reticulum/metabolism

KW - Gene Expression Regulation

KW - Insulin/metabolism

KW - Longevity

KW - Machado-Joseph Disease/metabolism

KW - Nerve Tissue Proteins/metabolism

KW - Ubiquitin/metabolism

M3 - SCORING: Journal article

VL - 13

SP - 273

EP - 281

JO - NAT CELL BIOL

JF - NAT CELL BIOL

SN - 1465-7392

IS - 3

M1 - 3

ER -