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
Citations
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Journal ArticleDOI
Classification of intrinsically disordered regions and proteins.
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Characterization of unannotated and uncharacterized protein segments is expected to lead to the discovery of novel functions as well as provide important insights into existing biological processes and is likely to shed new light on molecular mechanisms of diseases that are not yet fully understood.
Classification of Intrinsically Disordered Regions and Proteins
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Uncharacterized and uncharacterized protein segments are likely to be a large source of functional novelty relevant for discovering new biology as discussed by the authors, which is likely to lead to the discovery of novel functions as well as provide important insights into existing biological processes.
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Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1
Sue C. Bodine,Leslie M. Baehr +1 more
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.
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Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide
Eric S. Fischer,Kerstin Böhm,John R. Lydeard,Haidi Yang,Michael B. Stadler,Simone Cavadini,Jane Nagel,Fabrizio C. Serluca,Vincent Acker,Gondichatnahalli M. Lingaraju,Ritesh Bhanudasji Tichkule,Michael Schebesta,William C. Forrester,Markus Schirle,Ulrich Hassiepen,Johannes Ottl,Marc Hild,Rohan Eric John Beckwith,J. Wade Harper,Jeremy L. Jenkins,Nicolas H. Thomä +20 more
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.
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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
Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex
Wenyi Wei,Nagi G. Ayad,Yong Wan,Guo-Jun Zhang,Marc W. Kirschner,William G. Kaelin,William G. Kaelin +6 more
TL;DR: It is shown that the F-box protein Skp2 is polyubiquitinated, and hence earmarked for destruction, by APCCDH1, and accumulation of SCFSKP2 requires prior inactivation of APCC DH1.
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SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins
Luca Busino,Florian Bassermann,Alessio Maiolica,Choogon Lee,Patrick M. Nolan,Sofia I. H. Godinho,Giulio Draetta,Michele Pagano +7 more
TL;DR: It is found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCFFbxl3 ubiquitin ligase complex, a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity.
Journal ArticleDOI
The cell-cycle regulatory protein Cks1 is required for SCF Skp2 -mediated ubiquitinylation of p27
TL;DR: It is shown that the missing factor is CDK subunit 1 (Cks1), which belongs to the highly conserved Suc1/Cks family of proteins that bind to some CDKs and phosphorylated proteins and are essential for cell-cycle progression.
Journal ArticleDOI
Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis
Eric E. Zhang,Yi Liu,Yi Liu,Renaud Dentin,Pagkapol Y. Pongsawakul,Andrew C. Liu,Andrew C. Liu,Andrew C. Liu,Tsuyoshi Hirota,Tsuyoshi Hirota,Dmitri A. Nusinow,Xiujie Sun,Severine Landais,Yuzo Kodama,David A. Brenner,Marc Montminy,Steve A. Kay +16 more
TL;DR: It is shown that Creb activity during fasting is modulated by Cry1 and Cry2, which are rhythmically expressed in the liver, which suggest that compounds that enhance cryptochrome activity may provide therapeutic benefit to individuals with type 2 diabetes.
Journal ArticleDOI
Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase.
TL;DR: The induction of Skp2 and Cks1 degradation in G1 represents a principal mechanism by which APC/CCdh1 prevents the unscheduled degradation of SCFSkp2–Cks1 substrates and maintains the G1 state.
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