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  Cullin-RING Ubiquitin Ligase Regulatory Circuits: A Quarter Century Beyond the F-Box Hypothesis

Harper, J. W., & Schulman, B. A. (2021). Cullin-RING Ubiquitin Ligase Regulatory Circuits: A Quarter Century Beyond the F-Box Hypothesis. In Annual Review of Biochemistry, Vol 90, 2021 (pp. 403-429).

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 Creators:
Harper, J. Wade1, Author
Schulman, Brenda A.2, Author           
Affiliations:
1external, ou_persistent22              
2Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society, ou_2466699              

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Free keywords: STRUCTURAL BASIS; E3 LIGASE; CELL-CYCLE; COP9 SIGNALOSOME; SUBSTRATE RECOGNITION; PROTEOLYSIS MACHINERY; CONJUGATING ENZYMES; IRON HOMEOSTASIS; HIF-ALPHA; BETA-TRCPBiochemistry & Molecular Biology; cullin; cullin-RING ligase; ubiquitin; E3 ligase; NEDD8; F-box protein;
 Abstract: Cullin-RING ubiquitin ligases (CRLs) are dynamic modular platforms that regulate myriad biological processes through target-specific ubiquitylation. Our knowledge of this system emerged from the F-box hypothesis, posited a quarter century ago: Numerous interchangeable F-box proteins confer specific substrate recognition for a core CUL1-based RING E3 ubiquitin ligase. This paradigm has been expanded through the evolution of a superfamily of analogous modular CRLs, with five major families and over 200 different substrate-binding receptors in humans. Regulation is achieved by numerous factors organized in circuits that dynamically control CRL activation and substrate ubiquitylation. CRLs also serve as a vast landscape for developing small molecules that reshape interactions and promote targeted ubiquitylation-dependent turnover of proteins of interest. Here, we review molecular principles underlying CRL function, the role of allosteric and conformational mechanisms in controlling substrate timing and ubiquitylation, and how the dynamics of substrate receptor interchange drives the turnover of selected target proteins to promote cellular decision-making.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published in print
 Pages: 27
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Annual Review of Biochemistry, Vol 90, 2021
  Alternative Title : Annu. Rev. Biochem.
  Alternative Title : ANNU REV BIOCHEM
Source Genre: Proceedings
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: 403 - 429 Identifier: ISSN: 0066-4154
ISBN: 978-0-8243-0890-2

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Title: Annual Review of Biochemistry
  Alternative Title : ANNU REV BIOCHEM
  Alternative Title : Annu. Rev. Biochem..
Source Genre: Series
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: 90 Sequence Number: - Start / End Page: - Identifier: ISSN: 0066-4154