2. Academic Validation
  3. C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases

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

  • Mol Cell. 2018 May 17;70(4):602-613.e3. doi: 10.1016/j.molcel.2018.04.006.
Hsiu-Chuan Lin 1,  Chi-Wei Yeh 2,  Yen-Fu Chen 2,  Ting-Ting Lee 2,  Pei-Yun Hsieh 2,  Domnita V Rusnac 3,  Sung-Ya Lin 1,  Stephen J Elledge 4,  Ning Zheng 3,  Hsueh-Chi S Yen 5
Affiliations

Affiliations

  • 1 Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan.
  • 2 Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
  • 3 Howard Hughes Medical Institute, Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
  • 4 Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • 5 Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan. Electronic address: [email protected].
PMID: 29775578 DOI: 10.1016/j.molcel.2018.04.006
Abstract

The proteolysis-assisted protein quality control system guards the proteome from potentially detrimental aberrant proteins. How miscellaneous defective proteins are specifically eliminated and which molecular characteristics direct them for removal are fundamental questions. We reveal a mechanism, DesCEND (destruction via C-end degrons), by which CRL2 ubiquitin ligase uses interchangeable substrate receptors to recognize the unusual C termini of abnormal proteins (i.e., C-end degrons). C-end degrons are mostly less than ten residues in length and comprise a few indispensable residues along with some rather degenerate ones. The C-terminal end position is essential for C-end degron function. Truncated selenoproteins generated by translation errors and the USP1 N-terminal fragment from post-translational cleavage are eliminated by DesCEND. DesCEND also targets full-length proteins with naturally occurring C-end degrons. The C-end degron in DesCEND echoes the N-end degron in the N-end rule pathway, highlighting the dominance of protein "ends" as indicators for protein elimination.

Keywords

C-end degron; CRL2 ubiquitin ligase; DesCEND; protein quality control.

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