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All components of the UPP were predicted to be
2019-10-31
All components of the UPP were predicted to be susceptible to oxidative stress due to the cysteine residues in their active sites [36]. Curcusone D inhibits DUBs but has no significant effect on the action of E1, E2s, E3s, or the proteasome, which indicates that the targets of the ROS induced by cur
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br Acknowledgements The authors are supported by National In
2019-10-31
Acknowledgements The authors are supported by National Institutes of Health grants (CA162804, CA92584, and CA13499 to DJC and CA166677 to BPPC) and Cancer Prevention and Research Institute of Texas (RP110465 to DJC). The cellular response to DNA double-strand break (DSB) formation is an essent
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The authors gratefully acknowledge financial support from th
2019-10-31
The authors gratefully acknowledge financial support from the State of São Paulo Research Foundation (FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo), grants 2013/07600-3 and 2013/25658-9, and the National Council for Scientific and Technological Development (CNPq, Conselho Nacional d
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The on target in vitro pharmacology
2019-10-31
The on target in vitro pharmacology of 18 was then further explored, first in respect of murine CRTh2 receptor activity (Table 5), where similar levels of activity were found in both a binding and functional assay compared with the human orthologue, consistent with our earlier observations in the su
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br Materials and methods br Results br Discussion In
2019-10-31
Materials and methods Results Discussion In the past decade, GWAS have attempted to identify genetic variants that confer risk for many human diseases, whose inherited components remain unexplained (Manolio et al., 2009). In a few cases risk variants identified by GWAS have paved the way fo
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Although our knowledge of the
2019-10-30
Although our knowledge of the biochemical and biological functions of E3 ubiquitin ligases has increased in B-cell malignancies, a deeper characterization of cell-context dependent substrate regulation and biological relevance is needed. The recent approval of a general proteasome inhibitor, VELCADE
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Mono and bi ubiquitination of
2019-10-30
Mono- and bi-ubiquitination of two lysines, namely K70 and K76, in a small fraction of p33 replication co-factor has been demonstrated in yeast (Barajas and Nagy, 2010, Li et al., 2008). Because mutations of these lysines reduced TBSV repRNA replication in yeast and affected the ability of p33 to in
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Main Text Post translational modifications by ubiquitin
2019-10-30
Main Text Post-translational modifications by ubiquitin (Ub) and ubiquitin-like proteins (Ubl) regulate a diverse array of cellular and physiological processes including protein degradation, localization, and activation. While ubiquitination has primary responsibility for targeting substrates for p
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br Restenosis after angioplasty remains a remarkable challen
2019-10-30
Restenosis after angioplasty remains a remarkable challenge, although drug-eluting stents have reduced the incidence of restenosis considerably . Vascular smooth muscle dizocilpine (VSMCs) play a pivotal role in the development of intimal thickening and restenosis. VSMCs proliferate and migrate f
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br Funding br Conflict of interests br
2019-10-30
Funding Conflict of interests Introduction DAG is generated by the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) by PtdIns-specific phospholipase C (PLC) enzymes [1]. Remaining in the membrane, it binds proteins with cysteine-rich, C1 domains, and activates several of
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A 804598 Mitophagy is a selective autophagic process
2019-10-30
Mitophagy is a selective autophagic process which leads to the degradation of damaged mitochondria in response to metabolic or environmental stress conditions. In this study, we found that LFS-01 treatment significantly enhances p62 in a time-dependent manner. We found that the upregulation of p62 i
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Tinnitus Met carriers with severe hearing loss perceive thei
2019-10-30
Tinnitus Met carriers with severe hearing loss perceive their tinnitus as being louder, which is associated with increased activity in the PHC, increased PHC→pgACC connectivity, as well as decreased pgACC→PHC connectivity. This indicates that Met carriers with severe hearing loss have increased tinn
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br Author contribution br Acknowledgements We want to thank
2019-10-30
Author contribution Acknowledgements We want to thank Dr. Manuel Rodriguez, Dr. Ch. Blattner, Dr. Jorge Moscat, Dr. Erwin Knecht and Dr. Peter Tontonoz for materials. This work has been supported by grants from the Spanish Ministry of Education and ScienceSAF2011-27442 and a grant from General
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How does an increase in E affinity for
2019-10-30
How does an increase in E2 affinity for the RING domain favor higher activity and polyubiquitination by the E2? Binding of the RING domain to the E2 positions the donor Ub in the E2~Ub conjugate in a closed complex [16], [17], [18] that increases the reactivity of the thioester [60]. A higher affini
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The differences between ground and transition
2019-10-30
The differences between ground and transition state properties are exemplified by a comparison of our human–yeast results with those of a structural study of possible differences in ubiquitin-Uba-1 binding in yeast (known structure) with human (simulated in [12]). Their discussion focuses on Ubiquit
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