TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy

Autophagy. 2013 Dec;9(12):1955-64. doi: 10.4161/auto.26085.

Abstract

Upon completion of cytokinesis, the midbody ring is transported asymmetrically into one of the two daughter cells where it becomes a midbody ring derivative that is degraded by autophagy. In this study we showed that the ubiquitin-binding autophagy receptor SQSTM1/p62 and the interacting adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6 and that these proteins, as well as NBR1, are important for efficient clearance of midbody ring derivatives by autophagy. The number of ubiquitinated midbody ring derivatives decreases in TRAF6-depleted cells and we showed that TRAF6 mediates ubiquitination of the midbody ring localized protein KIF23/MKLP1. We conclude that TRAF6-mediated ubiquitination of the midbody ring is important for its subsequent recognition by ubiquitin-binding autophagy receptors and degradation by selective autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology
  • Autophagy / genetics*
  • Cells, Cultured
  • Cytokinesis / genetics*
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Microtubule-Associated Proteins / metabolism*
  • Proteins / physiology
  • Proteolysis
  • Sequestosome-1 Protein
  • TNF Receptor-Associated Factor 6 / physiology*
  • Ubiquitin / metabolism
  • Ubiquitination / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • KIF23 protein, human
  • Microtubule-Associated Proteins
  • NBR1 protein, human
  • Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • TNF Receptor-Associated Factor 6
  • Ubiquitin