TP53INP2 mediates autophagic degradation of ubiquitinated proteins through its ubiquitin-interacting motif

FEBS Lett. 2019 Aug;593(15):1974-1982. doi: 10.1002/1873-3468.13467. Epub 2019 Jun 20.

Abstract

The tumor protein p53-inducible nuclear protein 2 (TP53INP2) has been reported to participate in autophagy by interacting with autophagosome-localized autophagy-related protein 8 (Atg8) family proteins, including LC3. Here, we uncover a novel function for TP53INP2 in the autophagic degradation of proteins. We identify the ubiquitin-interacting motif (UIM) of TP53INP2 that mediates its binding to ubiquitin and ubiquitinated proteins. TP53INP2 lacking the UIM is able to displace autophagic adaptor p62 from LC3, which leads to accumulation of ubiquitinated proteins in cells. Furthermore, overexpression of TP53INP2 lacking the UIM sensitizes cells to chloroquine treatment. Our findings indicate that TP53INP2 may act as a novel autophagic adaptor through recruiting ubquitinated substrates to autophagosomes for degradation.

Keywords: LC3; TP53INP2; adaptor protein; autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Autophagosomes / metabolism*
  • Autophagy
  • Autophagy-Related Protein 8 Family / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Chloroquine / pharmacology
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Proteolysis
  • RNA-Binding Proteins / metabolism
  • Ubiquitin / metabolism*
  • Ubiquitinated Proteins / metabolism*
  • Up-Regulation

Substances

  • Autophagy-Related Protein 8 Family
  • GABARAPL2 protein, human
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • P62 protein, human
  • RNA-Binding Proteins
  • TP53INP2 protein, human
  • Ubiquitin
  • Ubiquitinated Proteins
  • Chloroquine