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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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Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1

TL;DR: This review will focus on the current understanding of MuRF1 and MAFbx in skeletal muscle, highlighting the critical questions that remain to be answered.
Journal ArticleDOI

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide

TL;DR: The studies suggest that IMiDs block endogenous substrates (MEIS2) from binding to CRL4CRBN while the ligase complex is recruiting IKZF1 or IKzF3 for degradation, which implies that small molecules can modulate an E3 ubiquitin ligase and thereby upregulate or downregulate the ubiquitination of proteins.
Journal ArticleDOI

New insights into ubiquitin E3 ligase mechanism

TL;DR: E3 ligases carry out the final step in the ubiquitination cascade, catalyzing transfer of ubiquitin from an E2 enzyme to form a covalent bond with a substrate lysine.
References
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Journal ArticleDOI

Composite low affinity interactions dictate recognition of the cyclin-dependent kinase inhibitor Sic1 by the SCFCdc4 ubiquitin ligase

TL;DR: It is shown that individually weak, dispersed Sic1 phospho sites engage CDC4 in a dynamic equilibrium, and phosphoepitope affinity for Cdc4 is dramatically weakened in the context of full-length Sic1, demonstrating the importance of regional environment on binding interactions.
Journal ArticleDOI

Structural Basis of Selective Ubiquitination of TRF1 by SCFFbx4

TL;DR: The results reveal an atypical small GTPase domain within Fbx4 as a substrate-binding motif for SCF(Fbx 4) and uncover a mechanism for selective ubiquitination and degradation of TRF1 in telomere homeostasis control.
Journal ArticleDOI

Interplay between poxviruses and the cellular ubiquitin/ubiquitin-like pathways

TL;DR: The various strategies used by poxviruses to target and subvert the host cell Ub/Ubl systems are described and discussed.
Journal ArticleDOI

Implication of the F-Box Protein FBXL21 in circadian pacemaker function in mammals.

TL;DR: Fbxl21 is established as a novel circadian clock-controlled gene that plays a specific role within the mammalian circadian pacemaker.
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