scholarly journals Drosophila mind bomb2 is required for maintaining muscle integrity and survival

2007 ◽  
Vol 179 (2) ◽  
pp. 219-227 ◽  
Author(s):  
Hanh T. Nguyen ◽  
Francesca Voza ◽  
Nader Ezzeddine ◽  
Manfred Frasch
Keyword(s):  
Muscle Development ◽  
Ubiquitin Ligases ◽  
Significant Degree ◽  
Mutant Phenotype ◽  
E3 Ubiquitin Ligases ◽  
Visceral Muscle ◽  
Apoptosis Markers ◽  
Somatic Muscles

We report that the Drosophila mind bomb2 (mib2) gene is a novel regulator of muscle development. Unlike its paralogue, mib1, zygotic expression of mib2 is restricted to somatic and visceral muscle progenitors, and their respective differentiated musculatures. We demonstrate that in embryos that lack functional Mib2, muscle detachment is observed beginning in mid stage 15 and progresses rapidly, culminating in catastrophic degeneration and loss of most somatic muscles by stage 17. Notably, the degenerating muscles are positive for apoptosis markers, and inhibition of apoptosis in muscles prevents to a significant degree the muscle defects. Rescue experiments with Mib1 and Neuralized show further that these E3 ubiquitin ligases are not capable of ameliorating the muscle mutant phenotype of mib2. Our data suggest strongly that mib2 is involved in a novel Notch- and integrin-independent pathway that maintains the integrity of fully differentiated muscles and prevents their apoptotic degeneration.

Twist and Notch negatively regulate adult muscle differentiation in Drosophila

Development ◽  
1998 ◽  
Vol 125 (8) ◽  
pp. 1361-1369 ◽  
Author(s):  
S. Anant ◽  
S. Roy ◽  
K. Vijay Raghavan
Keyword(s):  
Cell Fate ◽  
Muscle Development ◽  
Flight Muscle ◽  
Mutant Phenotype ◽  
Indirect Flight Muscle ◽  
Adult Muscle ◽  
Drosophila Embryogenesis ◽  
Twist Expression ◽  
Somatic Muscles

Twist is required in Drosophila embryogenesis for mesodermal specification and cell-fate choice. We have examined the role of Twist and Notch during adult indirect flight muscle development. Reduction in levels of Twist leads to abnormal myogenesis. Notch reduction causes a similar mutant phenotype and reduces Twist levels. Conversely, persistent expression, in myoblasts, of activated Notch causes continued twist expression and failure of differentiation as assayed by myosin expression. The gain-of-function phenotype of Notch is very similar to that seen upon persistent twist expression. These results point to a relationship between Notch function and twist regulation during indirect flight muscle development and show that decline in Twist levels is a requirement for the differentiation of these muscles, unlike the somatic muscles of the embryo.

Regulation of Epithelial-Mesenchymal Transition by E3 Ubiquitin Ligases and Deubiquitinase in Cancer

2016 ◽  
Vol 16 (2) ◽  
pp. 110-118 ◽  
Author(s):  
Yasumichi Inoue ◽  
Yuka Itoh ◽  
Koichi Sato ◽  
Fumihiro Kawasaki ◽  
Chihiro Sumita ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Mesenchymal Transition

scholarly journals Ubiquitination, Biotech Startups, and the Future of TRIM Family Proteins: A TRIM-Endous Opportunity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1015
Author(s):  
Utsa Bhaduri ◽  
Giuseppe Merla
Keyword(s):  
Drug Discovery ◽  
Protein Degradation ◽  
Ubiquitin Ligase ◽  
Genetic Disorders ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Post Translational Modification ◽  
Disease Biology ◽  
The Future

Ubiquitination is a post-translational modification that has pivotal roles in protein degradation and diversified cellular processes, and for more than two decades it has been a subject of interest in the biotech or biopharmaceutical industry. Tripartite motif (TRIM) family proteins are known to have proven E3 ubiquitin ligase activities and are involved in a multitude of cellular and physiological events and pathophysiological conditions ranging from cancers to rare genetic disorders. Although in recent years many kinds of E3 ubiquitin ligases have emerged as the preferred choices of big pharma and biotech startups in the context of protein degradation and disease biology, from a surface overview it appears that TRIM E3 ubiquitin ligases are not very well recognized yet in the realm of drug discovery. This article will review some of the blockbuster scientific discoveries and technological innovations from the world of ubiquitination and E3 ubiquitin ligases that have impacted the biopharma community, from biotech colossuses to startups, and will attempt to evaluate the future of TRIM family proteins in the province of E3 ubiquitin ligase-based drug discovery.

scholarly journals TRIM32 and Malin in Neurological and Neuromuscular Rare Diseases

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 820
Author(s):  
Lorena Kumarasinghe ◽  
Lu Xiong ◽  
Maria Adelaida Garcia-Gimeno ◽  
Elisa Lazzari ◽  
Pascual Sanz ◽  
...  
Keyword(s):  
Common Ancestor ◽  
Genetic Diseases ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Lafora Disease ◽  
C Terminus ◽  
Rare Genetic Diseases ◽  
Tripartite Motif ◽  
Trim Proteins ◽  
Ring E3

Tripartite motif (TRIM) proteins are RING E3 ubiquitin ligases defined by a shared domain structure. Several of them are implicated in rare genetic diseases, and mutations in TRIM32 and TRIM-like malin are associated with Limb-Girdle Muscular Dystrophy R8 and Lafora disease, respectively. These two proteins are evolutionary related, share a common ancestor, and both display NHL repeats at their C-terminus. Here, we revmniew the function of these two related E3 ubiquitin ligases discussing their intrinsic and possible common pathophysiological pathways.

scholarly journals Regulation of Notch signaling by E3 ubiquitin ligases

FEBS Journal ◽  
2021 ◽  
Author(s):  
Debdeep Dutta ◽  
Vartika Sharma ◽  
Mousumi Mutsuddi ◽  
Ashim Mukherjee
Keyword(s):  
Notch Signaling ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases

scholarly journals Comprehensive database of human E3 ubiquitin ligases: application to aquaporin-2 regulation

2016 ◽  
Vol 48 (7) ◽  
pp. 502-512 ◽  
Author(s):  
Barbara Medvar ◽  
Viswanathan Raghuram ◽  
Trairak Pisitkun ◽  
Abhijit Sarkar ◽  
Mark A. Knepper
Keyword(s):  
Human Genome ◽  
Large Scale ◽  
E3 Ligase ◽  
Ubiquitin Ligases ◽  
Bayes Rule ◽  
E3 Ubiquitin Ligases ◽  
E3 Ligases ◽  
Aquaporin 2 ◽  
Large Scale Data ◽  
Level Data

Aquaporin-2 (AQP2) is regulated in part via vasopressin-mediated changes in protein half-life that are in turn dependent on AQP2 ubiquitination. Here we addressed the question, “What E3 ubiquitin ligase is most likely to be responsible for AQP2 ubiquitination?” using large-scale data integration based on Bayes' rule. The first step was to bioinformatically identify all E3 ligase genes coded by the human genome. The 377 E3 ubiquitin ligases identified in the human genome, consisting predominant of HECT, RING, and U-box proteins, have been used to create a publically accessible and downloadable online database ( https://hpcwebapps.cit.nih.gov/ESBL/Database/E3-ligases/ ). We also curated a second database of E3 ligase accessory proteins that included BTB domain proteins, cullins, SOCS-box proteins, and F-box proteins. Using Bayes' theorem to integrate information from multiple large-scale proteomic and transcriptomic datasets, we ranked these 377 E3 ligases with respect to their probability of interaction with AQP2. Application of Bayes' rule identified the E3 ligases most likely to interact with AQP2 as (in order of probability): NEDD4 and NEDD4L (tied for first), AMFR, STUB1, ITCH, ZFPL1. Significantly, the two E3 ligases tied for top rank have also been studied extensively in the reductionist literature as regulatory proteins in renal tubule epithelia. The concordance of conclusions from reductionist and systems-level data provides strong motivation for further studies of the roles of NEDD4 and NEDD4L in the regulation of AQP2 protein turnover.

E3 ubiquitin ligases as T cell anergy factors

2004 ◽  
Vol 5 (9) ◽  
pp. 883-890 ◽  
Author(s):  
Daniel L Mueller
Keyword(s):  
T Cell ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
T Cell Anergy ◽  
Cell Anergy
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