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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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Design Principles Involving Protein Disorder Facilitate Specific Substrate Selection and Degradation by the Ubiquitin-Proteasome System.

TL;DR: The role of structural disorder and conformational flexibility in the different aspects of degradation are reviewed and biochemical experiments and predictions show that initiation of degradation at the 26S proteasome requires a partially unfolded region to facilitate substrate entry into the proteasomal core.
Journal ArticleDOI

GGTase3 is a Newly Identified Geranylgeranyltransferase Targeting a Ubiquitin Ligase

TL;DR: The previously unknown human prenyltransferase, GGTase3, geranylgeranylates the ubiquitin ligase FBXL2, which bears a motif predicted to be recognized by GGT enzyme, calling for a revision of the ‘prenylation code’.
Journal ArticleDOI

Plant ubiquitin ligases as signaling hubs.

TL;DR: Plants have imparted valuable lessons about the pharmacology of ubiquitin modification, with structural analysis providing mechanistic insights into how hormone perception and signaling are coupled to protein ubiquitination.
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...
Journal ArticleDOI

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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