Transgenic manipulation of the ubiquitin–proteasome system

2005 ◽  
Vol 41 ◽  
pp. 129-138
Author(s):  
Douglas A. Gray
Keyword(s):  
Mouse Model ◽  
Basic Research ◽  
Ubiquitin Proteasome System ◽  
Industrial Applications ◽  
Model Systems ◽  
Transgenic Organisms ◽  
Plant Nematode ◽  
Ubiquitin Proteasome ◽  
Research Questions ◽  
Transgenic Manipulation

The transgenic approach has been used in model systems from yeast to mammals to address basic research questions, and to achieve agricultural, pharmaceutical or industrial objectives. In basic research, transgenic organisms have generated novel observations that could not have been obtained otherwise. This chapter concentrates on the use of transgenics in deciphering the operation of the UPS (ubiquitin–proteasome system) in the yeast, plant, nematode, fly, and mouse model systems, and will touch on ways in which transgenic manipulation of the UPS has been exploited for agricultural, pharmaceutical, and industrial applications.

A novel transgenic mouse model reveals deregulation of the ubiquitin‐proteasome system in the heart by doxorubicin

2005 ◽  
Vol 19 (14) ◽  
pp. 2051-2053 ◽  
Author(s):  
Asangi R. K. Kumarapeli ◽  
Kathleen M. Horak ◽  
Joseph W. Glasford ◽  
Jie Li ◽  
Quanhai Chen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Ubiquitin Proteasome System ◽  
Transgenic Mouse Model ◽  
Ubiquitin Proteasome

scholarly journals Systematic approaches to identify E3 ligase substrates

2016 ◽  
Vol 473 (22) ◽  
pp. 4083-4101 ◽  
Author(s):  
Mary Iconomou ◽  
Darren N. Saunders
Keyword(s):  
Cell Cycle Progression ◽  
Target Identification ◽  
Ubiquitin Proteasome System ◽  
Model Systems ◽  
Covalent Attachment ◽  
Post Translational Modification ◽  
Diverse Range ◽  
E3 Ligases ◽  
Ubiquitin Proteasome ◽  
Substrate Proteins

Protein ubiquitylation is a widespread post-translational modification, regulating cellular signalling with many outcomes, such as protein degradation, endocytosis, cell cycle progression, DNA repair and transcription. E3 ligases are a critical component of the ubiquitin proteasome system (UPS), determining the substrate specificity of the cascade by the covalent attachment of ubiquitin to substrate proteins. Currently, there are over 600 putative E3 ligases, but many are poorly characterized, particularly with respect to individual protein substrates. Here, we highlight systematic approaches to identify and validate UPS targets and discuss how they are underpinning rapid advances in our understanding of the biochemistry and biology of the UPS. The integration of novel tools, model systems and methods for target identification is driving significant interest in drug development, targeting various aspects of UPS function and advancing the understanding of a diverse range of disease processes.

A transgenic mouse model of the ubiquitin/proteasome system

2003 ◽  
Vol 21 (8) ◽  
pp. 897-902 ◽  
Author(s):  
Kristina Lindsten ◽  
Victoria Menéndez-Benito ◽  
Maria G Masucci ◽  
Nico P Dantuma
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Ubiquitin Proteasome System ◽  
Transgenic Mouse Model ◽  
Ubiquitin Proteasome

scholarly journals Oxidative stress regulates the ubiquitin–proteasome system and immunoproteasome functioning in a mouse model of X-adrenoleukodystrophy

Brain ◽  
2013 ◽  
Vol 136 (3) ◽  
pp. 891-904 ◽  
Author(s):  
Nathalie Launay ◽  
Montserrat Ruiz ◽  
Stéphane Fourcade ◽  
Agatha Schlüter ◽  
Cristina Guilera ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome

scholarly journals SUFFICIENT ACTIVITY OF THE UBIQUITIN PROTEASOME SYSTEM IN AGED MICE AND DURING RETINAL DEGENERATION SUPPORTS DHFR-BASED CONDITIONAL CONTROL OF PROTEIN ABUNDANCE IN THE RETINA

2021 ◽  
Author(s):  
Hui Peng ◽  
Prerana Ramadurgum ◽  
DaNae R. Woodard ◽  
Steffi Daniel ◽  
Marian Renwick ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Mouse Models ◽  
Ubiquitin Proteasome System ◽  
Model Systems ◽  
Protein Abundance ◽  
Aged Mice ◽  
Gene Therapies ◽  
Conditional Control ◽  
Ubiquitin Proteasome ◽  
Regulate Protein

SummaryThe Escherichia coli dihydrofolate reductase (DHFR) destabilizing domain (DD) serves as a promising approach to conditionally regulate protein abundance in a variety of tissues. In the absence of TMP, a DHFR stabilizer, the DD is degraded by the ubiquitin proteasome system (UPS). To test whether this approach could be effectively applied to a wide variety of aged and disease-related ocular mouse models, which may have a compromised UPS, we evaluated the DHFR DD system in aged mice (up to 24 mo), a light-induced retinal degeneration (LIRD) model, and two genetic models of retinal degeneration (rd2 and Abca4−/− mice). Aged, LIRD, and Abca4−/− mice all had similar proteasomal activities and high-molecular weight ubiquitin levels compared to control mice. However, rd2 mice displayed compromised chymotrypsin activity compared to control mice. Nonetheless, the DHFR DD was effectively degraded in all model systems, including rd2 mice. Moreover, TMP increased DHFR DD-dependent retinal bioluminescence in all mouse models, however the fold induction was slightly, albeit significantly, lower in Abca4−/− mice. Thus, the destabilized DHFR DD-based approach allows for efficient control of protein abundance in aged mice and retinal degeneration mouse models, laying the foundation to use this strategy in a wide variety of mice for the conditional control of gene therapies to potentially treat multiple eye diseases.

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