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Mechanisms and function of substrate recruitment by F-box proteins

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TLDR
The evolution of substrate recruitment by F-box proteins, the dysregulation of substrates in disease and potential avenues for F- box protein-directed disease therapies are focused on.
Abstract
S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) ubiquitin ligase complexes use a family of F-box proteins as substrate adaptors to mediate the degradation of a large number of regulatory proteins involved in diverse processes The dysregulation of SCF complexes and their substrates contributes to multiple pathologies In the 14 years since the identification and annotation of the F-box protein family, the continued identification and characterization of novel substrates has greatly expanded our knowledge of the regulation of substrate targeting and the roles of F-box proteins in biological processes Here, we focus on the evolution of our understanding of substrate recruitment by F-box proteins, the dysregulation of substrate recruitment in disease and potential avenues for F-box protein-directed disease therapies

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AtMYB93 is an endodermis-specific transcriptional regulator of lateral root development in arabidopsis

TL;DR: Recent findings in the wider context of root system development are discussed – with a particular focus on the role of the endodermis - and several potential models to explain AtMYB93 function during lateral root organogenesis are proposed.
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NS5A Promotes Constitutive Degradation of IP3R3 to Counteract Apoptosis Induced by Hepatitis C Virus.

TL;DR: An IP3-independent molecular mechanism through which HCV promotes IP3R3 degradation, thereby inhibiting virus-induced apoptosis and establishing chronic infection is revealed.
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Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler.

TL;DR: Use of synthetic ubiquitins with non-natural acceptor site replacements reveals that the aliphatic side chain specifying reactive amine geometry is a determinant of the ubiquitin code, through unanticipated and complex reliance of many distinct Ubiquitin-carrying enzymes on a canonical acceptor lysine.
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Identification of Key Regulatory Genes and Pathways in Prefrontal Cortex of Alzheimer’s Disease

TL;DR: Several genes and pathways that play critical roles in PFC of AD patients have been uncovered, which will provide novel insights on molecular targets for treatment and diagnostic biomarkers of AD.
Journal ArticleDOI

Characterization of a cytoplasmic glucosyltransferase that extends the core trisaccharide of the Toxoplasma Skp1 E3 ubiquitin ligase subunit.

TL;DR: This work found that Toxoplasma utilizes a cytoplasmic glycosyltransferase from an ancient clade of CAZy family GT32 to catalyze transfer of the fourth sugar, and found that glt1-knock-out parasites exhibited a growth defect not rescued by catalytically inactive Glt1, indicating that the glycan acts in concert with the first enzyme in the pathway, PhyA, in cells.
References
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Journal ArticleDOI

The Ubiquitin System

TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
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Wnt/β-catenin signaling: components, mechanisms, and diseases

TL;DR: Some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis are highlighted, and potential therapeutic implications are discussed.
Journal ArticleDOI

The Ubiquitin Code

TL;DR: The structure, assembly, and function of the posttranslational modification with ubiquitin, a process referred to as ubiquitylation, controls almost every process in cells.
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