scholarly journals Autophagy promotes synapse development in Drosophila

2009 ◽  
Vol 187 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Wei Shen ◽  
Barry Ganetzky
Keyword(s):  
Stress Responses ◽  
Degradation Mechanism ◽  
Ubiquitin Proteasome System ◽  
Dominant Negative ◽  
Environmental Cues ◽  
Biological Processes ◽  
Synaptic Growth ◽  
Cellular Stress Responses ◽  
Ubiquitin Proteasome ◽  
Larval Neuromuscular Junction

Autophagy, a lysosome-dependent degradation mechanism, mediates many biological processes, including cellular stress responses and neuroprotection. In this study, we demonstrate that autophagy positively regulates development of the Drosophila melanogaster larval neuromuscular junction (NMJ). Autophagy induces an NMJ overgrowth phenotype closely resembling that of highwire (hiw), an E3 ubiquitin ligase mutant. Moreover, like hiw, autophagy-induced NMJ overgrowth is suppressed by wallenda (wnd) and by a dominant-negative c-Jun NH2-terminal kinase (bskDN). We show that autophagy promotes NMJ growth by reducing Hiw levels. Thus, autophagy and the ubiquitin–proteasome system converge in regulating synaptic development. Because autophagy is triggered in response to many environmental cues, our findings suggest that it is perfectly positioned to link environmental conditions with synaptic growth and plasticity.

Degradation of mutant huntingtin via the ubiquitin/proteasome system is modulated by FE65

2012 ◽  
Vol 443 (3) ◽  
pp. 681-689 ◽  
Author(s):  
Wan Ning Vanessa Chow ◽  
Hon Wing Luk ◽  
Ho Yin Edwin Chan ◽  
Kwok-Fai Lau
Keyword(s):  
Cell Death ◽  
Degradation Mechanism ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Adaptor Protein ◽  
Ubiquitin Proteasome System ◽  
Exon 1 ◽  
Ubiquitin Proteasome

An unstable expansion of the polyglutamine repeat within exon 1 of the protein Htt (huntingtin) causes HD (Huntington's disease). Mounting evidence shows that accumulation of N-terminal mutant Htt fragments is the source of disruption of normal cellular processes which ultimately leads to neuronal cell death. Understanding the degradation mechanism of mutant Htt and improving its clearance has emerged as a new direction in developing therapeutic approaches to treat HD. In the present study we show that the brain-enriched adaptor protein FE65 is a novel interacting partner of Htt. The binding is mediated through WW–polyproline interaction and is dependent on the length of the polyglutamine tract. Interestingly, a reduction in mutant Htt protein level was observed in FE65-knockdown cells, and the process requires the UPS (ubiquitin/proteasome system). Moreover, the ubiquitination level of mutant Htt was found to be enhanced when FE65 is knocked down. Immunofluroescence staining revealed that FE65 associates with mutant Htt aggregates. Additionally, we demonstrated that overexpression of FE65 increases mutant Htt-induced cell death both in vitro and in vivo. These results suggest that FE65 facilitates the accumulation of mutant Htt in cells by preventing its degradation via the UPS, and thereby enhances the toxicity of mutant Htt.

scholarly journals More Than Just Cleaning: Ubiquitin-Mediated Proteolysis in Fungal Pathogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Chengjun Cao ◽  
Chaoyang Xue
Keyword(s):  
Stress Responses ◽  
Fungal Infections ◽  
Proteasome Inhibitors ◽  
Field Research ◽  
Pathogenic Fungi ◽  
Ubiquitin Proteasome System ◽  
Fungal Pathogenesis ◽  
Regulatory Function ◽  
Pathogenic Factors ◽  
Ubiquitin Proteasome

Ubiquitin-proteasome mediated protein turnover is an important regulatory mechanism of cellular function in eukaryotes. Extensive studies have linked the ubiquitin-proteasome system (UPS) to human diseases, and an array of proteasome inhibitors have been successfully developed for cancer therapy. Although still an emerging field, research on UPS regulation of fungal development and virulence has been rapidly advancing and has generated considerable excitement in its potential as a target for novel drugs. In this review, we summarize UPS composition and regulatory function in pathogenic fungi, especially in stress responses, host adaption, and fungal pathogenesis. Emphasis will be given to UPS regulation of pathogenic factors that are important for fungal pathogenesis. We also discuss future potential therapeutic strategies for fungal infections based on targeting UPS pathways.

scholarly journals Proteasome-associated ubiquitin ligase relays target plant hormone-specific transcriptional activators

2021 ◽  
Author(s):  
Zhishuo Wang ◽  
Beatriz Orosa-Puente ◽  
Mika Nomoto ◽  
Heather Grey ◽  
Thomas Potuschak ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Stress Responses ◽  
Plant Hormone ◽  
Ubiquitin Ligases ◽  
Ubiquitin Proteasome System ◽  
Transcriptional Activators ◽  
Sequential Action ◽  
Ubiquitin Proteasome ◽  
Universal Mechanism ◽  
Target Plant

The ubiquitin-proteasome system is vital to hormone-mediated developmental and stress responses in plants. Ubiquitin ligases target hormone-specific transcriptional activators (TAs) for degradation, but how TAs are processed by proteasomes remains unknown. We report that in Arabidopsis the salicylic acid- and ethylene-responsive TAs, NPR1 and EIN3, are relayed from pathway-specific ubiquitin ligases to proteasome-associated HECT-type UPL3/4 ligases. Activity and stability of NPR1 was regulated by sequential action of three ubiquitin ligases, including UPL3/4, while proteasome processing of EIN3 required physical handover between ethylene-responsive SCFEBF2 and UPL3/4 ligases. Consequently, UPL3/4 controlled extensive hormone-induced developmental and stress-responsive transcriptional programmes. Thus, our findings identify unknown ubiquitin ligase relays that terminate with proteasome-associated HECT-type ligases, which may be a universal mechanism for processive degradation of proteasome-targeted TAs and other substrates.

scholarly journals Emerging Roles of the Selective Autophagy in Plant Immunity and Stress Tolerance

2020 ◽  
Vol 21 (17) ◽  
pp. 6321
Author(s):  
Jie Ran ◽  
Sayed M. Hashimi ◽  
Jian-Zhong Liu
Keyword(s):  
Abiotic Stress ◽  
Stress Tolerance ◽  
Plant Immunity ◽  
Abiotic Stress Tolerance ◽  
Ubiquitin Proteasome System ◽  
Biological Processes ◽  
Related Gene ◽  
Biotic And Abiotic Stress ◽  
Selective Autophagy ◽  
Ubiquitin Proteasome

Autophagy is a conserved recycling system required for cellular homeostasis. Identifications of diverse selective receptors/adaptors that recruit appropriate autophagic cargoes have revealed critical roles of selective autophagy in different biological processes in plants. In this review, we summarize the emerging roles of selective autophagy in both biotic and abiotic stress tolerance and highlight the new features of selective receptors/adaptors and their interactions with both the cargoes and Autophagy-related gene 8s (ATG8s). In addition, we review how the two major degradation systems, namely the ubiquitin–proteasome system (UPS) and selective autophagy, are coordinated to cope with stress in plants. We especially emphasize how plants develop the selective autophagy as a weapon to fight against pathogens and how adapted pathogens have evolved the strategies to counter and/or subvert the immunity mediated by selective autophagy.

scholarly journals Interaction between the Circadian Clock and Regulators of Heat Stress Responses in Plants

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 156
Author(s):  
Tejasvinee Mody ◽  
Titouan Bonnot ◽  
Dawn H. Nagel
Keyword(s):  
Gene Regulation ◽  
Transcription Factors ◽  
Heat Stress ◽  
Circadian Clock ◽  
Temperature Stress ◽  
Stress Responses ◽  
Environmental Cues ◽  
Biological Processes ◽  
Regulatory Pathways ◽  
Response To Temperature

The circadian clock is found ubiquitously in nature, and helps organisms coordinate internal biological processes with environmental cues that inform the time of the day or year. Both temperature stress and the clock affect many important biological processes in plants. Specifically, clock-controlled gene regulation and growth are impacted by a compromised clock or heat stress. The interactions linking these two regulatory pathways include several rhythmic transcription factors that are important for coordinating the appropriate response to temperature stress. Here we review the current understanding of clock control of the regulators involved in heat stress responses in plants.

scholarly journals Role of Eicosanoids in Regulating the Ubiquitin Proteasome System and Proteostasis

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Amanpreet Kaur
Keyword(s):  
Degradation Mechanism ◽  
Protein A ◽  
Chimeric Protein ◽  
Ubiquitin Proteasome System ◽  
Protein Homeostasis ◽  
Intercellular Signaling ◽  
Wild Type ◽  
Signaling Mechanisms ◽  
Ubiquitin Proteasome

The ubiquitin proteasome system (UPS) is a protein degradation mechanism in eukaryotes crucial to maintaining protein homeostasis, or proteostasis. There are tissue-specific differences in UPS activity and proteostasis, but the intercellular signaling mechanisms that mediate these differences are not well understood. This work examines eicosanoid signaling molecules—which are derived from polyunsaturated fatty acids (PUFAs)—and their role in proteostasis regulation, particularly the UPS. A reporter transgene that expresses the UbG76V-GFP chimeric protein, a metastable substrate for the UPS, is used in Caenorhabditis elegans epithelial cells to monitor the level of UPS activity. In wild-type nematodes, UbG76V-GFP levels remain high through 24 hours post L4 stage (L4+24). Then, levels decrease significantly due to increased UPS activity as the animals age and develop 48 hours past L4 (L4+48). Mutants for fat-1, a desaturase enzyme that converts ω-6 PUFAs to ω-3 PUFAs, exhibited elevated UbG76V-GFP turnover in the hypodermis even at the L4+24 stage, suggesting that either ω-6 PUFAs (or their eicosanoid derivatives) promote UPS activity or ω-3 PUFAs (or their eicosanoid derivatives) inhibit UPS activity. In the intestine, mutants for fat-1 showed reduced UbG76V-GFP turnover at the L4+24 and L4+48 life stages. Additionally, mutants for emb-8—an NADPH reductase needed to convert PUFAs into eicosanoids—also showed reduced UbG76V-GFP turnover in the hypodermis even at the L4+48 stage. These results suggest that elements of the eicosanoid signaling pathway, including ω-6 PUFAs and their derivatives, significantly contribute to regulation of the UPS and proteostasis.

scholarly journals SPAAC Pulse-Chase: A Novel Click Chemistry-Based Method to Determine the Half-Life of Cellular Proteins

2021 ◽  
Vol 9 ◽  
Author(s):  
Trevor M. Morey ◽  
Mohammad Ali Esmaeili ◽  
Martin L. Duennwald ◽  
R. Jane Rylett
Keyword(s):  
Click Chemistry ◽  
Stress Responses ◽  
Half Life ◽  
Yeast Cells ◽  
Cellular Proteins ◽  
Biological Processes ◽  
Life Measurement ◽  
Cellular Stress Responses ◽  
Endogenous Proteins ◽  
The Stability

Assessing the stability and degradation of proteins is central to the study of cellular biological processes. Here, we describe a novel pulse-chase method to determine the half-life of cellular proteins that overcomes the limitations of other commonly used approaches. This method takes advantage of pulse-labeling of nascent proteins in living cells with the bioorthogonal amino acid L-azidohomoalanine (AHA) that is compatible with click chemistry-based modifications. We validate this method in both mammalian and yeast cells by assessing both over-expressed and endogenous proteins using various fluorescent and chemiluminescent click chemistry-compatible probes. Importantly, while cellular stress responses are induced to a limited extent following live-cell AHA pulse-labeling, we also show that this response does not result in changes in cell viability and growth. Moreover, this method is not compromised by the cytotoxicity evident in other commonly used protein half-life measurement methods and it does not require the use of radioactive amino acids. This new method thus presents a versatile, customizable, and valuable addition to the toolbox available to cell biologists to determine the stability of cellular proteins.

The ubiquitin–proteasome system and skeletal muscle wasting

2005 ◽  
Vol 41 ◽  
pp. 173-186 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Proteolytic Enzymes ◽  
Cathepsin L ◽  
Ubiquitin Proteasome System ◽  
Complete Breakdown ◽  
Skeletal Muscle Proteins ◽  
Ubiquitin Proteasome ◽  
Tripeptidyl Peptidase Ii ◽  
F Box Protein

The ubiquitin–proteasome system (UPS) is believed to degrade the major contractile skeletal muscle proteins and plays a major role in muscle wasting. Different and multiple events in the ubiquitination, deubiquitination and proteolytic machineries are responsible for the activation of the system and subsequent muscle wasting. However, other proteolytic enzymes act upstream (possibly m-calpain, cathepsin L, and/or caspase 3) and downstream (tripeptidyl-peptidase II and aminopeptidases) of the UPS, for the complete breakdown of the myofibrillar proteins into free amino acids. Recent studies have identified a few critical proteins that seem necessary for muscle wasting {i.e. the MAFbx (muscle atrophy F-box protein, also called atrogin-1) and MuRF-1 [muscle-specific RING (really interesting new gene) finger 1] ubiquitin–protein ligases}. The characterization of their signalling pathways is leading to new pharmacological approaches that can be useful to block or partially prevent muscle wasting in human patients.

The ubiquitin–proteasome system and skeletal muscle wasting

2005 ◽  
Vol 41 (1) ◽  
pp. 173 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Ubiquitin Proteasome System ◽  
Skeletal Muscle Wasting ◽  
Ubiquitin Proteasome
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