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Substrate Recognition by the Cdh1 Destruction Box Receptor Is a General Requirement for APC/CCdh1-mediated

Liang Qin1, Dimitrius Santiago P S F Guimarães1, Michael Melesse1

  • 1From the Department of Biochemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.

The Journal of Biological Chemistry
|May 27, 2016
PubMed

Insights

The anaphase-promoting complex (APC/C) targets proteins for degradation. This study reveals that the D-box receptor is crucial for all APC/C-Cdh1 substrate degradation, even those lacking canonical D-boxes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The anaphase-promoting complex/cyclosome (APC/C) is a critical ubiquitin ligase regulating the eukaryotic cell cycle.
  • APC/C controls protein degradation during mitosis and G1 phase.
  • Substrate recognition by APC/C is not fully understood, with known motifs like D-box and KEN-box not present in all substrates.

Purpose of the Study:

  • To investigate the mechanisms of APC/C substrate recognition and degradation.
  • To determine the role of different degron motifs (D-box, KEN-box, ABBA) in APC/C-Cdh1 substrate processing.
  • To identify essential recognition pathways for APC/C substrates lacking canonical degrons.

Main Methods:

  • Utilized an in vivo yeast assay to assess protein degradation rates.
  • Compared degradation of 15 known APC/C-Cdh1 substrates under varying conditions.
  • Manipulated conditions to impair the binding of D-box, KEN-box, and ABBA motifs to Cdh1.

Main Results:

  • The D-box receptor was essential for the efficient proteolysis of all tested Cdh1 substrates.
  • Many substrates degraded efficiently despite lacking canonical D-boxes.
  • The KEN-box and ABBA motif receptors played roles in a subset and single substrate, respectively.

Conclusions:

  • D-box receptor binding appears to be a universal requirement for Cdh1-mediated APC/C substrate recognition and degradation.
  • Alternative or incomplete degron definitions may exist for APC/C substrates.
  • This finding refines our understanding of cell cycle control and protein turnover.
Keywords:
APC/CCdh1Cdh1KEN boxanaphase-promoting complexcell cycledestruction boxprotein degradationprotein stabilityubiquitin ligaseubiquitylation (ubiquitination)

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