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| http://dx.doi.org/10.1016/j.gendis.2022.02.004 | DOI Listing |
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SPT5 regulates RNA polymerase II stability via Cullin 3-ARMC5 recognition.
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Simpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
The stability of RNA polymerase II (Pol II) is tightly regulated during transcriptional elongation for proper control of gene expression. Our recent studies revealed that promoter-proximal Pol II is destabilized via the ubiquitin E3 ligase cullin 3 (CUL3) upon loss of transcription elongation factor SPT5. Here, we investigate how CUL3 recognizes chromatin-bound Pol II as a substrate.
View Article and Find Full Text PDFLeveraging Structural and Computational Biology for Molecular Glue Discovery.
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Experimental Drug Development Centre, Chromos, Agency for Science, Technology and Research, 10 Biopolis Road, #05-01, Singapore 138670.
The discovery of molecular glues has made significant strides, unlocking new avenues for targeted protein degradation as a therapeutic strategy, thereby expanding the scope of drug discovery into territories previously considered undruggable. Pioneering molecules like thalidomide and its derivatives have paved the way for the development of small molecules that can induce specific protein degradation by hijacking the cellular ubiquitin-proteasome system. Recent advancements have focused on expanding the range of E3 ligases and target proteins that can be modulated by molecular glues.
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Faculty of Bioscience Engineering, Ghent University, Gent, Belgium.
In the coevolutionary process between plant pathogens and hosts, pathogen effectors, primarily proteinaceous, engage in interactions with host proteins, such as plant transcription factors (TFs), during the infection process. This review delves into the intricate interplay between TFs and effectors, a key aspect in the prolonged and complex battle between plants and pathogens. Effectors strategically manipulate TFs using diverse tactics.
View Article and Find Full Text PDFUSP39 promotes retinal pathological angiogenesis in retinopathy of prematurity by stabilizing SIRT2 expression through deubiquitination.
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Department of Ophthalmology, Xingtai People's Hospital, Xingtai, 054001, Hebei, China.
Background: Retinopathy of prematurity (ROP) is a major cause of childhood blindness worldwide, highlighted by retinal neovascularization. Ubiquitin is present throughout the retina. The deubiquitinating enzyme ubiquitin-specific protease 39 (USP39) has been reported to be involved in angiogenesis.
View Article and Find Full Text PDFDysregulation of Metabolic Peptides Precedes Hyperinsulinemia and Inflammation Following Exposure to Rotenone in Rats.
Cells
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Ralph H. Johnson Veterans Administration Medical Center, 109 Bee Street, Charleston, SC 29401, USA.
Rotenone, a naturally occurring compound derived from the roots of tropical plants, is used as a broad-spectrum insecticide, piscicide, and pesticide. It is a classical, high-affinity mitochondrial complex I inhibitor that causes not only oxidative stress, α-synuclein phosphorylation, DJ-1 (Parkinson's disease protein 7) modifications, and inhibition of the ubiquitin-proteasome system but it is also widely considered an environmental contributor to Parkinson's disease (PD). While prodromal symptoms, such as loss of smell, constipation, sleep disorder, anxiety/depression, and the loss of dopaminergic neurons in the substantia nigra of rotenone-treated animals, have been reported, alterations of metabolic hormones and hyperinsulinemia remain largely unknown and need to be investigated.
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