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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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Journal ArticleDOI

GCL and CUL3 Control the Switch between Cell Lineages by Mediating Localized Degradation of an RTK.

TL;DR: It is shown that Drosophila Germ cell-less (GCL) is a critical component in this process by acting as a switch that turns off a somatic lineage pathway by mediating degradation of Torso and defines cell fate at the single-cell level.
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A Novel Function of F-Box Protein FBXO17 in Negative Regulation of Type I IFN Signaling by Recruiting PP2A for IFN Regulatory Factor 3 Deactivation

TL;DR: It is found that FBXO17 specifically interacts with IFN regulatory factor 3 (IRF3) and decreases its dimerization and nuclear translocation and a novel mechanism for IRF3 deactivation by F-box protein-mediated recruitment of PP2A is demonstrated.
Journal ArticleDOI

Regulation of Ubiquitin-like with Plant Homeodomain and RING Finger Domain 1 (UHRF1) Protein Stability by Heat Shock Protein 90 Chaperone Machinery.

TL;DR: Evidence that UHRF1 interacts with HSP90 chaperone complex and is a novel H SP90 client protein is presented and light is shed on the regulation of U HRF1 stability and function.
Journal ArticleDOI

Targeting the Nuclear Export Protein XPO1/CRM1 Reverses Epithelial to Mesenchymal Transition.

TL;DR: It is demonstrated for the first time that targeted inhibition of nuclear exporter protein exportin 1 (XPO1) by Selective Inhibitor of Nuclear Export (SINE) compounds results in reversal of EMT in snail-transduced primary human mammary epithelial cells (HMECs).
Journal ArticleDOI

FBXL5 targets cortactin for ubiquitination-mediated destruction to regulate gastric cancer cell migration.

TL;DR: It is reported thatFBXL5 interacts with and targets cortactin for ubiquitylation and subsequent proteasomal degradation, and it is shown that FBXL5-induced cortact in gastric cancer cells migration is mediated by extracellular regulated signal kinase (ERK).
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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