2. Academic Validation
  3. K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking

K33-Linked Polyubiquitination of Coronin 7 by Cul3-KLHL20 Ubiquitin E3 Ligase Regulates Protein Trafficking

  • Mol Cell. 2014 May 22;54(4):586-600. doi: 10.1016/j.molcel.2014.03.035.
Wei-Chien Yuan 1,  Yu-Ru Lee 2,  Shu-Yu Lin 2,  Li-Ying Chang 2,  Yen Pei Tan 2,  Chin-Chun Hung 2,  Jean-Cheng Kuo 3,  Cheng-Hsin Liu 2,  Mei-Yao Lin 2,  Ming Xu 4,  Zhijian J Chen 4,  Ruey-Hwa Chen 5
Affiliations

Affiliations

  • 1 Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 106, Taiwan.
  • 2 Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
  • 3 Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 112, Taiwan.
  • 4 Department of Molecular Biology, Howard Hughes Medical Institute, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
  • 5 Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 106, Taiwan. Electronic address: rhchen@gate.sinica.edu.tw.
PMID: 24768539 DOI: 10.1016/j.molcel.2014.03.035
Abstract

Ubiquitin chains are formed as structurally distinct Polymers via different linkages, and several chain types including K33-linkage remain uncharacterized. Here, we describe a role for K33-polyubiquitination in protein trafficking. We show that the Cullin 3 (Cul3) substrate adaptor KLHL20 is localized to the trans-Golgi network (TGN) and is important for post-Golgi trafficking by promoting the biogenesis of TGN-derived transport carriers. The Cul3-KLHL20 ubiquitin E3 Ligase catalyzes a nondegradable, K33-linked polyubiquitination on coronin 7 (Crn7), which facilitates Crn7 targeting to TGN through a ubiquitin-dependent interaction with Eps15. Blockage of K33-chain formation, Crn7 ubiquitination, or disruption of Crn7-Eps15 interaction impairs TGN-pool F-actin assembly, a process essential for generating transport carriers. Enforced targeting of Crn7 to TGN bypasses the requirement of K33-ubiquitination for TGN-pool F-actin assembly and post-Golgi trafficking. Our study reveals a role of KLHL20-mediated K33-ubiquitination of Crn7 in post-Golgi transport and identifies a cellular recognition mechanism for this ubiquitin chain type.

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