Ubiquitination

Publication Title: 
Cell Cycle (Georgetown, Tex.)

Macroautophagy is a self-cannibalistic process that enables cells to adapt to various stresses and maintain energy homeostasis. Additionally, autophagy is an important route for turnover of misfolded proteins and damaged organelles, with important implications in cancer, neurodegenerative diseases and aging. Resveratrol and spermidine are able to induce autophagy by affecting deacetylases and acetylases, respectively, and have been found to extend the life-span of model organisms.

Author(s): 
Bennetzen, Martin V.
MariÒo, Guillermo
Pultz, Dennis
Morselli, Eugenia
FÊrgeman, Nils J.
Kroemer, Guido
Andersen, Jens S.
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: 
PloS One

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. Mutations in superoxide dismutase (SOD1) are associated with familial ALS and lead to SOD1 protein misfolding and aggregation. Here we show that the molecular chaperone, HSJ1 (DNAJB2), mutations in which cause distal hereditary motor neuropathy, can reduce mutant SOD1 aggregation and improve motor neuron survival in mutant SOD1 models of ALS.

Author(s): 
Novoselov, Sergey S.
Mustill, Wendy J.
Gray, Anna L.
Dick, James R.
Kanuga, Naheed
Kalmar, Bernadett
Greensmith, Linda
Cheetham, Michael E.
Publication Title: 
Molecular and Cellular Biology

The ubiquitin ligase CHIP (carboxyl terminus of Hsp70-interacting protein) regulates protein quality control, and CHIP deletion accelerates aging and reduces the life span in mice. Here, we reveal a mechanism for CHIP's influence on longevity by demonstrating that CHIP stabilizes the sirtuin family member SirT6, a lysine deacetylase/ADP ribosylase involved in DNA repair, metabolism, and longevity.

Author(s): 
Ronnebaum, Sarah M.
Wu, Yaxu
McDonough, Holly
Patterson, Cam
Publication Title: 
Genes & Development

The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex possesses acetyltransferase and deubiquitinase activities. Within this modular complex, Ataxin-7 anchors the deubiquitinase activity to the larger complex. Here we identified and characterized Drosophila Ataxin-7 and found that reduction of Ataxin-7 protein results in loss of components from the SAGA complex.

Author(s): 
Mohan, Ryan D.
Dialynas, George
Weake, Vikki M.
Liu, Jianqi
Martin-Brown, Skylar
Florens, Laurence
Washburn, Michael P.
Workman, Jerry L.
Abmayr, Susan M.
Publication Title: 
Developmental Cell

Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF(DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1.

Author(s): 
Horn, Moritz
Geisen, Christoph
Cermak, Lukas
Becker, Ben
Nakamura, Shuhei
Klein, Corinna
Pagano, Michele
Antebi, Adam
Publication Title: 
Nature Structural & Molecular Biology
Author(s): 
Kevei, …va
Hoppe, Thorsten
Publication Title: 
Epigenomics

Huntington's disease is a late-onset, autosomal dominant neurodegenerative disorder characterized by motor, cognitive and psychiatric symptomatology. The earliest stage of Huntington's disease is marked by alterations in gene expression, which partially results from dysregulated epigenetic modifications.

Author(s): 
Wang, Fengli
Fischhaber, Paula L.
Guo, Caixia
Tang, Tie-Shan
Publication Title: 
The American Journal of Pathology

Ubiquitinated endosomal proteins that are deposited into the lumens of multivesicular bodies are either sorted for lysosomal-mediated degradation or secreted as exosomes into the extracellular milieu. The mechanisms that underlie the sorting of cellular cargo proteins are currently unknown. In this study, we show that the COP9 signalosome (CSN)-associated protein CSN5 quantitatively regulated proteins that were sorted into exosomes.

Author(s): 
Liu, Yuelong
Shah, Spandan V.
Xiang, Xiaoyu
Wang, Jianhua
Deng, Zhong-Bin
Liu, Cunren
Zhang, Liming
Wu, Jianming
Edmonds, Tara
Jambor, Christina
Kappes, John C.
Zhang, Huang-Ge
Publication Title: 
The Biochemical Journal

Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that activates transcription of a battery of cytoprotective genes by binding to the ARE (antioxidant response element). Nrf2 is repressed by the cysteine-rich Keap1 (kelch-like ECH-associated protein 1) protein, which targets Nrf2 for ubiquitination and subsequent degradation by a Cul3 (cullin 3)-mediated ubiquitination complex. We find that modification of Cys(151) of human Keap1, by mutation to a tryptophan, relieves the repression by Keap1 and allows activation of the ARE by Nrf2.

Author(s): 
Eggler, Aimee L.
Small, Evan
Hannink, Mark
Mesecar, Andrew D.

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