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
The F-Box Domain-Dependent Activity of EMI1 Regulates PARPi Sensitivity in Triple-Negative Breast Cancers.
Antonio Marzio,J Puccini,Youngho Kwon,Natalia Maverakis,Arnaldo A. Arbini,Patrick Sung,Dafna Bar-Sagi,Michele Pagano +7 more
TL;DR: Reconstitution of EMI1 expression reestablishes PARPi sensitivity both in cellular systems and in an orthotopic mouse model.
Journal ArticleDOI
Design Principles Involving Protein Disorder Facilitate Specific Substrate Selection and Degradation by the Ubiquitin-Proteasome System.
TL;DR: The role of structural disorder and conformational flexibility in the different aspects of degradation are reviewed and biochemical experiments and predictions show that initiation of degradation at the 26S proteasome requires a partially unfolded region to facilitate substrate entry into the proteasomal core.
Journal ArticleDOI
GGTase3 is a Newly Identified Geranylgeranyltransferase Targeting a Ubiquitin Ligase
Shafi Kuchay,Hui Wang,Antonio Marzio,Kunj Jain,Harrison Homer,Nicole Fehrenbacher,Mark R. Philips,Ning Zheng,Michele Pagano +8 more
TL;DR: The previously unknown human prenyltransferase, GGTase3, geranylgeranylates the ubiquitin ligase FBXL2, which bears a motif predicted to be recognized by GGT enzyme, calling for a revision of the ‘prenylation code’.
Journal ArticleDOI
Plant ubiquitin ligases as signaling hubs.
Nitzan Shabek,Ning Zheng +1 more
TL;DR: Plants have imparted valuable lessons about the pharmacology of ubiquitin modification, with structural analysis providing mechanistic insights into how hormone perception and signaling are coupled to protein ubiquitination.
Journal ArticleDOI
KELCH F-BOX protein positively influences Arabidopsis seed germination by targeting PHYTOCHROME-INTERACTING FACTOR1.
Manoj Majee,Santosh Kumar,Praveen Kumar Kathare,Shuiqin Wu,Derek J. Gingerich,Nihar R. Nayak,Louai Salaita,Randy D. Dinkins,Kathleen M. Martin,Michael M. Goodin,Lynnette M.A. Dirk,Taylor D. Lloyd,Ling Zhu,Joseph Chappell,Arthur G. Hunt,Richard D. Vierstra,Enamul Huq,A. Bruce Downie +17 more
TL;DR: It is proposed that PIF1 and CTG10 coexist, and even accumulate, in the nucleus in darkness, but that, following illumination, CTG 10 assists in reducing PIF 1 amounts, thus promoting the completion of seed germination and subsequent seedling development.
References
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The Mutational Landscape of Head and Neck Squamous Cell Carcinoma
Nicolas Stransky,Ann Marie Egloff,Aaron D. Tward,Aaron D. Tward,Aaron D. Tward,Aleksandar Kostic,Aleksandar Kostic,Kristian Cibulskis,Andrey Sivachenko,Gregory Kryukov,Gregory Kryukov,Michael S. Lawrence,Carrie Sougnez,Aaron McKenna,Erica Shefler,Alex H. Ramos,Petar Stojanov,Scott L. Carter,Douglas Voet,Maria L. Cortes,Daniel Auclair,Michael F. Berger,Gordon Saksena,Candace Guiducci,Robert C. Onofrio,Melissa Parkin,Marjorie Romkes,Joel L. Weissfeld,Raja R. Seethala,Lin Wang,Claudia Rangel-Escareño,Juan Carlos Fernández-López,Alfredo Hidalgo-Miranda,Jorge Melendez-Zajgla,Wendy Winckler,Kristin Ardlie,Stacey Gabriel,Matthew Meyerson,Eric S. Lander,Eric S. Lander,Eric S. Lander,Gad Getz,Todd R. Golub,Levi A. Garraway,Jennifer R. Grandis +44 more
TL;DR: In this article, the authors analyzed whole-exome sequencing data from 74 tumor-normal pairs and found that at least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis.
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