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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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Targeting prenylation inhibition through the mevalonate pathway.

TL;DR: Progress towards the development of inhibitors against the prenylation machinery is highlighted, including antagonizing the upstream mevalonate pathway enzymes, FPPS and GGPPS, which mediate prenyation as well as cholesterol synthesis.
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SCF FBXW17 E3 ubiquitin ligase regulates FBXL19 stability and cell migration.

TL;DR: It is discovered that a new ubiquitin E3 ligase, SCFFBXW17, ubiquitinates and induces FBXL19 degradation, which promotes cell migration and downregulation ofFBXL19 attenuated lysophosphatidic acid‐induced lamellipodia formation and Rac1 accumulation at migration leading edge.
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Pan- and core- network analysis of co-expression genes in a model plant

TL;DR: By analyzing 134 microarray datasets for Arabidopsis, it is found that gene coexpression networks are highly context-dependent.
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Lnx2b, an E3 ubiquitin ligase, in dorsal forerunner cells and Kupffer's vesicle is required for specification of zebrafish left–right laterality

TL;DR: It is reported that Lnx2b, a RING domain containing E3 Ub ligase, specifically expressed in migratory DFCs and developing KV, plays a critical role in the establishment of LR laterality in zebrafish embryos.
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Latency-Associated Nuclear Antigen E3 Ubiquitin Ligase Activity Impacts Gammaherpesvirus-Driven Germinal Center B Cell Proliferation.

TL;DR: It is demonstrated that the E3 ligase activity of mLANA contributes to gammaherpesvirus-driven GC B cell proliferation, and pharmacological inhibition of viral E3ligase activity through targeting SOCS box motifs is a putative strategy to control gammaherpev virus-driven lymphoproliferation and associated disease.
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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