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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Dissertation
Identification of new regulators for PML nuclear bodies
TL;DR: This thesis project was to identify new regulators of PML Nuclear Bodies, and by extension of the SUMO pathway, using PML-NBs, which are extremely sensitive to global cellular SUMOylation level, as a read out, and identified FBXO9 as the F-Box capable of specifically recognizing PML, causing its ubiquitination by SCFFBxO9 complex and subsequent degradation by the proteasome.
References
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TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
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TL;DR: These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling.
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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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