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.
Journal ArticleDOI
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
More filters
Journal ArticleDOI
Composite low affinity interactions dictate recognition of the cyclin-dependent kinase inhibitor Sic1 by the SCFCdc4 ubiquitin ligase
Xiaojing Tang,Stephen Orlicky,Tanja Mittag,Veronika Csizmok,Tony Pawson,Julie D. Forman-Kay,Frank Sicheri,Mike Tyers +7 more
TL;DR: It is shown that individually weak, dispersed Sic1 phospho sites engage CDC4 in a dynamic equilibrium, and phosphoepitope affinity for Cdc4 is dramatically weakened in the context of full-length Sic1, demonstrating the importance of regional environment on binding interactions.
Journal ArticleDOI
The Glomuvenous Malformation Protein Glomulin Binds Rbx1 and Regulates Cullin RING Ligase-Mediated Turnover of Fbw7
Adriana E. Tron,Takehiro Arai,Takehiro Arai,David M. Duda,Hiroshi Kuwabara,Hiroshi Kuwabara,Jennifer L. Olszewski,Yuko Fujiwara,Yuko Fujiwara,Brittany Bahamon,Sabina Signoretti,Brenda A. Schulman,James A. DeCaprio,James A. DeCaprio +13 more
TL;DR: It is shown that Glomulin (Glmn), a protein found mutated in the vascular disorder glomuvenous malformation (GVM), binds directly to the RING domain of Rbx1 and inhibits its E3 ubiquitin ligase activity.
Journal ArticleDOI
Structural Basis of Selective Ubiquitination of TRF1 by SCFFbx4
Zhixiong Zeng,Wei Wang,Yuting Yang,Yong Chen,Xiaomei Yang,Xiaomei Yang,J. Alan Diehl,Xuedong Liu,Ming Lei +8 more
TL;DR: The results reveal an atypical small GTPase domain within Fbx4 as a substrate-binding motif for SCF(Fbx 4) and uncover a mechanism for selective ubiquitination and degradation of TRF1 in telomere homeostasis control.
Journal ArticleDOI
Interplay between poxviruses and the cellular ubiquitin/ubiquitin-like pathways
TL;DR: The various strategies used by poxviruses to target and subvert the host cell Ub/Ubl systems are described and discussed.
Journal ArticleDOI
Implication of the F-Box Protein FBXL21 in circadian pacemaker function in mammals.
TL;DR: Fbxl21 is established as a novel circadian clock-controlled gene that plays a specific role within the mammalian circadian pacemaker.
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