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.
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