Ubiquitin

Publication Title: 
Journal of Biochemistry

FOXO (Forkhead box O) transcription factors constitute an evolutionally conserved subgroup within the large Forkhead family of transcription regulators. FOXO factors are important regulators of the cell cycle, apoptosis, DNA repair, metabolism, oxidative stress resistance and longevity. Genetic studies of Caenorhabditis elegans demonstrated that FOXO factors are major targets of the insulin-like signalling implicated during the regulation of glucose metabolism and lifespan extension.

Author(s): 
Daitoku, Hiroaki
Fukamizu, Akiyoshi
Publication Title: 
Nature Cell Biology

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).

Author(s): 
Kuhlbrodt, Kirsten
Janiesch, Philipp Christoph
Kevei, …va
Segref, Alexandra
Barikbin, Roja
Hoppe, Thorsten
Publication Title: 
PLoS genetics

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking.

Author(s): 
Kruegel, Undine
Robison, Brett
Dange, Thomas
Kahlert, G¸nther
Delaney, Joe R.
Kotireddy, Soumya
Tsuchiya, Mitsuhiro
Tsuchiyama, Scott
Murakami, Christopher J.
Schleit, Jennifer
Sutphin, George
Carr, Daniel
Tar, Krisztina
Dittmar, Gunnar
Kaeberlein, Matt
Kennedy, Brian K.
Schmidt, Marion
Publication Title: 
PloS One

Deubiquitinating enzymes (DUBs) are proteases that control the post-translational modification of proteins by ubiquitin and in turn regulate diverse cellular pathways. Despite a growing understanding of DUB biology at the structural and molecular level, little is known about the physiological importance of most DUBs. Here, we systematically identify DUBs encoded by the genome of Drosophila melanogaster and examine their physiological importance in vivo. Through domain analyses we uncovered 41 Drosophila DUBs, most of which have human orthologues.

Author(s): 
Tsou, Wei-Ling
Sheedlo, Michael J.
Morrow, Marie E.
Blount, Jessica R.
McGregor, Kelly M.
Das, Chittaranjan
Todi, Sokol V.
Publication Title: 
Annual Review of Genetics

The fruit fly, Drosophila melanogaster, is an excellent organism for the study of the genetic and molecular basis of metazoan development. Drosophila provides numerous tools and reagents to unravel the molecular and cellular functions of genes that cause human disease, and the past decade has witnessed a significant expansion of the study of neurodegenerative disease mechanisms in flies. Here we review the interplay between oxidative stress and neuronal toxicity.

Author(s): 
Jaiswal, M.
Sandoval, H.
Zhang, K.
Bayat, V.
Bellen, H. J.
Publication Title: 
Aging Cell

Coordinated expression of mitochondrial and nuclear genes is required to maintain proper mitochondrial function. However, the precise mechanisms that ensure this coordination are not well defined. We find that signaling from mitochondria to the nucleus is influenced by mammalian target of rapamycin (mTOR) activity via changes in autophagy and p62/SQSTM1 turnover. Reducing mTOR activity increases autophagic flux, enhances mitochondrial membrane potential, reduces reactive oxygen species within the cell, and increases replicative life span.

Author(s): 
Lerner, Chad
Bitto, Alessandro
Pulliam, Daniel
Nacarelli, Timothy
Konigsberg, Mina
Van Remmen, Holly
Torres, Claudio
Sell, Christian
Publication Title: 
Nature Structural & Molecular Biology
Author(s): 
Kevei, …va
Hoppe, Thorsten
Publication Title: 
Annals of the New York Academy of Sciences

Aging is characterized by accumulation of potentially harmful altered proteins that could lead to gradual deterioration of cellular functions and eventually result in increased probability of death. Metabolic turnover of proteins thus plays an essential role in maintaining the life of an organism. In this article we summarize our current knowledge on age-related changes in protein turnover with special reference to degradation. Increase in half-life of proteins with advancing age is well documented.

Author(s): 
Goto, S.
Takahashi, R.
Kumiyama, A. A.
Rad·k, Z.
Hayashi, T.
Takenouchi, M.
Abe, R.
Publication Title: 
Seikagaku. The Journal of Japanese Biochemical Society
Author(s): 
Daitoku, Hiroaki
Fukamizu, Akiyoshi
Publication Title: 
Molecular Microbiology

Artemisinin- and artesunate-resistant Plasmodium chabaudi mutants, AS-ART and AS-ATN, were previously selected from chloroquine-resistant clones AS-30CQ and AS-15CQ respectively. Now, a genetic cross between AS-ART and the artemisinin-sensitive clone AJ has been analysed by Linkage Group Selection. A genetic linkage group on chromosome 2 was selected under artemisinin treatment. Within this locus, we identified two different mutations in a gene encoding a deubiquitinating enzyme.

Author(s): 
Hunt, Paul
Afonso, Ana
Creasey, Alison
Culleton, Richard
Sidhu, Amar Bir Singh
Logan, John
Valderramos, Stephanie G.
McNae, Iain
Cheesman, Sandra
do Rosário, Virgílio
Carter, Richard
Fidock, David A.
Cravo, Pedro

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