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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

O2 sensing–associated glycosylation exposes the F-box–combining site of the Dictyostelium Skp1 subunit in E3 ubiquitin ligases

TL;DR: An unprecedented view of how a glycan modification influences a disordered region of a full-length protein is offered and the increased sampling of an open Skp1 conformation can explain how glycosylation enhances interactions with F-box proteins in cells.
Journal ArticleDOI

A cullin-RING ubiquitin ligase promotes thermotolerance as part of the intracellular pathogen response in Caenorhabditis elegans

TL;DR: These findings show that maintaining protein homeostasis may be a critical component of a multifaceted approach allowing the host to deal with stress caused by intracellular infection, and adds to the understanding of how organisms cope with proteotoxic stress.
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Molecular Factors Involved in Spinal Muscular Atrophy Pathways as Possible Disease-modifying Candidates.

TL;DR: Study of factors influencing SMN2 expression enables to reveal mechanisms underlying SMA pathology and can have pronounced clinical application.
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FBXO31 protects against genomic instability by capping FOXM1 levels at the G2/M transition.

TL;DR: F-box proteins in conjunction with Skp1, Cul1 and Rbx1 generate SCF complexes that are responsible for the ubiquitination of proteins, leading to their activation or degradation, and FBXO31 is the first described negative regulator of FOXM1 during the G2/M transition.
Journal ArticleDOI

Regulation of the ubiquitylation and deubiquitylation of CREB-binding protein modulates histone acetylation and lung inflammation.

TL;DR: These findings delineate the molecular mechanisms through which CBP stability is regulated by FBXL19 and USP14, which results in the modulation of chromatin remodeling and the expression of cytokine-encoding genes.
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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