Autophagy controls centrosome number by degrading Cep63

Nat Commun. 2016 Nov 21:7:13508. doi: 10.1038/ncomms13508.

Abstract

Centrosome number is associated with the chromosome segregation and genomic stability. The ubiquitin-proteasome system is considered to be the main regulator of centrosome number. However, here we show that autophagy also regulates the number of centrosomes. Autophagy-deficient cells carry extra centrosomes. The autophagic regulation of centrosome number is dependent on a centrosomal protein of 63 (Cep63) given that cells lacking autophagy contain multiple Cep63 dots that are engulfed and digested by autophagy in wild-type cells, and that the upregulation of Cep63 increases centrosome number. Cep63 is recruited to autophagosomes via interaction with p62, a molecule crucial for selective autophagy. In vivo, hematopoietic cells from autophagy-deficient and p62-/- mice also contained multiple centrosomes. These results indicate that autophagy controls centrosome number by degrading Cep63.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Protein 5 / metabolism
  • Autophagy-Related Protein 7 / genetics
  • Autophagy-Related Protein 7 / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Centrosome*
  • Humans
  • Mice
  • Mice, Knockout
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Sequestosome-1 Protein / genetics
  • Sequestosome-1 Protein / metabolism

Substances

  • Atg5 protein, mouse
  • Atg7 protein, mouse
  • Autophagy-Related Protein 5
  • CEP63 protein, human
  • Cell Cycle Proteins
  • Cep63 protein, mouse
  • Neoplasm Proteins
  • Sequestosome-1 Protein
  • Sqstm1 protein, mouse
  • Autophagy-Related Protein 7