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C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases

Hsiu-Chuan Lin1, Chi-Wei Yeh2, Yen-Fu Chen2

  • 1Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan.

Molecular Cell
|May 19, 2018
PubMed

Insights

The DesCEND pathway uses C-end degrons to eliminate aberrant proteins via the CRL2 ubiquitin ligase. This mechanism targets proteins with unusual C termini, similar to the N-end rule pathway.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Protein quality control is vital for cellular health, preventing the accumulation of harmful aberrant proteins.
  • Understanding the mechanisms of selective protein degradation is crucial for comprehending cellular homeostasis.

Purpose of the Study:

  • To elucidate the mechanism by which the CRL2 ubiquitin ligase system recognizes and eliminates defective proteins.
  • To identify the molecular determinants that target proteins for degradation via their C termini.

Main Methods:

  • Identification and characterization of the DesCEND pathway.
  • Analysis of C-end degron structure and function.
  • Investigating the role of CRL2 ubiquitin ligase and its substrate receptors.

Main Results:

  • A novel degradation pathway, DesCEND (destruction via C-end degrons), was revealed.
  • DesCEND utilizes interchangeable substrate receptors within the CRL2 ubiquitin ligase complex to recognize unusual C termini (C-end degrons).
  • C-end degrons are short sequences, typically under ten residues, with essential and degenerate components, critically dependent on their C-terminal position.

Conclusions:

  • DesCEND mediates the elimination of truncated selenoproteins and USP1 fragments, as well as full-length proteins with natural C-end degrons.
  • The C-end degron mechanism parallels the N-end rule pathway, emphasizing the significance of protein "ends" in degradation signaling.
  • This discovery provides fundamental insights into proteolysis-assisted protein quality control.
Keywords:
C-end degronCRL2 ubiquitin ligaseDesCENDprotein quality control

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