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#ubiquitin ligase

3 public questions tagged with this topic.

Cell Cycle Regulation

The APC/C-Cdh1 complex is required for:

Specificity and timing of APC/C activity arise from sequential association with two adaptors, Cdc20 and Cdh1, both containing seven WD40 repeats forming beta-propeller that binds D-box and KEN motifs. During prometaphase and metaphase, APC/C-Cdc20 polyubiquitinates securin and cyclin B to trigger anaphase and mitotic exit. At telophase, cyclin B degradation reduces CDK1 activity, allowing Cdc14 phosphatase to dephosphorylate Cdh1, enabling its binding to APC/C core. APC/C-Cdh1 then operates from late mitosis through entire G1, continuously ubiquitinating mitotic cyclins A and B, mitotic kinase

Ref: Peters, Nature Reviews Mol Cell Biol 2006, APC/C Mechanisms. Alberts 7th ed., Chapter 17.

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Cell Cycle Regulation

The SCF complex is primarily responsible for:

SCF complex forms prototypical cullin-RING ubiquitin ligase governing G1/S and S-phase progression, distinct from mitotic APC/C. Architecture comprises scaffold Cullin1, adaptor Skp1, RING finger Rbx1 recruiting E2 ubiquitin conjugating enzyme, and interchangeable F-box protein providing substrate specificity through WD40 or leucine-rich repeats. Activity regulated by substrate phosphorylation creating phosphodegron that interacts with F-box. During late G1, Cdk2-Cyclin E phosphorylates cyclin-dependent kinase inhibitor p27 Kip1 at Thr187, Sic1 ortholog in yeast at multiple CDK sites and p21 a

Ref: Cardozo & Pagano, SCF Ubiquitin Ligases Regulate Cell Cycle, Nat Rev Mol Cell Biol 2004; Frescas & Pagano, SCF Functions in G1/S Control.

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Cell Cycle Regulation

During mitosis, which event is triggered by APC/C activation?

Transition into anaphase is driven by activation of anaphase promoting complex cyclosome bound to Cdc20, a large 1.2 MDa cullin-RING E3 ubiquitin ligase. When SAC is satisfied, MCC disassembly through p31comet and TRIP13 releases Cdc20 permitting association with APC/C core. Active APC/C-Cdc20 recognizes destruction box degrons on two pivotal substrates: securin and Cyclin B. Polyubiquitination of securin triggers rapid proteolysis via 26S proteasome, discharging separase cysteine protease previously held inactive as pseudosubstrate. Free separase cleaves Scc1 or Rad21 kleisin subunit of cohes

Ref: Pines, APC/C Regulation of Anaphase Onset, Nat Rev Mol Cell Biol 2011; NCBI Bookshelf, Anaphase Triggered by APC/C.

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