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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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Visualizing ubiquitination in mammalian cells

TL;DR: The progress in direct and indirect imaging of differentially linked ubiquitin chains in fixed and living cells using confocal fluorescence microscopy and super‐resolution microscopy is discussed, illustrated by the role of ubiquitIn in antibacterial autophagy and pro‐inflammatory signalling.
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A genome-scale CRISPR-Cas9 screening in myeloma cells identifies regulators of immunomodulatory drug sensitivity

TL;DR: It is demonstrated that CSN9 signalosome complex regulates sensitivity to IMiDs by modulating CRBN expression, and pretreatment with either proteasome inhibitors or NEDD8 activating enzyme (NAE) inhibitors can abrogate degradation and maintain levels of CRBN, thereby enhancing sensitivity toIMiDs.
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Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mammalian Cell Differentiation.

TL;DR: It is proposed here that CRL3 complexes evolved to fulfill a pivotal role in mammalian cell differentiation and often associate with chromatin to control DNA metabolism.
Journal ArticleDOI

FBXO22 Possesses Both Protumorigenic and Antimetastatic Roles in Breast Cancer Progression.

TL;DR: The findings uncover an unexpected dual role for FBXO22 in mammary tumorigenesis and metastatic progression and delineate the mechanism of an oncogenic mutation of FBXo22 in breast cancer progression.
Journal ArticleDOI

Structural dynamics of the human COP9 signalosome revealed by cross-linking mass spectrometry and integrative modeling.

TL;DR: A structural model is proposed in which CSN9 binding triggers CSN to adopt a configuration that facilitates CSN–CRL interactions, thereby augmenting CSN deneddylase activity and generalized to define in-solution architectures of dynamic protein complexes that remain inaccessible to other approaches.
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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