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 therapiesread more
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Journal ArticleDOI
Glycosylation Promotes the Random Coil to Helix Transition in a Region of a Protist Skp1 Associated with F-Box Binding.
TL;DR: Glycosylation may control F-box protein interactions via a local effect on DdSkp1 conformation, by a mechanism that may be general to many unicellular eukaryotes.
Journal ArticleDOI
FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway.
Xiaoxia Che,Fangfang Jian,Ying Wang,Jingjing Zhang,Jian Shen,Qi Cheng,Xi Wang,Nan Jia,Weiwei Feng +8 more
TL;DR: It is concluded that FBXO2 acts as an E3 ligase that targets FBN1 for ubiquitin-dependent degradation, so as to promote EC proliferation by regulating the cell cycle and the autophagy signaling pathway.
Journal ArticleDOI
An Amyotrophic Lateral Sclerosis-Associated Mutant of C21ORF2 Is Stabilized by NEK1-Mediated Hyperphosphorylation and the Inability to Bind FBXO3.
Yasuaki Watanabe,Tadashi Nakagawa,Tetsuya Akiyama,Makiko Nakagawa,Naoki Suzuki,Hitoshi Warita,Masashi Aoki,Keiko Nakayama +7 more
TL;DR: It is suggested that inhibition of NEK1 activity is a potential therapeutic approach to ALS associated with C21ORF2 mutation by showing that FBXO3, the substrate receptor of an SCF ubiquitin ligase complex, binds and ubiquitylates C21 ORF2, thereby targeting it for proteasomal degradation.
Journal ArticleDOI
CRISPR/Cas9 Screens Reveal Multiple Layers of B cell CD40 Regulation
Chang Jiang,Chang Jiang,Stephen J. Trudeau,Stephen J. Trudeau,Taek-Chin Cheong,Rui Guo,Rui Guo,Mingxiang Teng,Liang Wei Wang,Liang Wei Wang,Zhonghao Wang,Zhonghao Wang,Zhonghao Wang,Chiara Pighi,Chiara Pighi,Carole Gautier-Courteille,Carole Gautier-Courteille,Yijie Ma,Yijie Ma,Sizun Jiang,Sizun Jiang,Chong Wang,Bo Zhao,Luc Paillard,Luc Paillard,John G. Doench,Roberto Chiarle,Roberto Chiarle,Benjamin E. Gewurz +28 more
TL;DR: To systematically identify B cell autonomous CD40 regulators, CRISPR/Cas9 genome-scale screens in Daudi B cells stimulated by multimeric CD40 ligand highlight known CD40 pathway components and reveal multiple additional mechanisms regulating CD40.
Journal ArticleDOI
FBXL7 Upregulation Predicts a Poor Prognosis and Associates with a Possible Mechanism for Paclitaxel Resistance in Ovarian Cancer
Hui-Wen Chiu,Jeng-Shou Chang,Hui-Yu Lin,Hsun-Hua Lee,Chia-Hao Kuei,Che-Hsuan Lin,Huei-Mei Huang,Yuan Feng Lin +7 more
TL;DR: It is found that FBXL7 was downregulated in OVSAHO (PTX-sensitive) but upregulated in KURAMOCHI ( PTX-resistant) cells after PTX treatment at cytotoxic concentrations, andFBXL7 may be a useful biomarker for predicting complete pathologic response in ovarian cancer patients who decide to receive post-operative PTX therapy.
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