The E3 ubiquitin ligase Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability

FEBS Lett. 2015 Jan 2;589(1):94-101. doi: 10.1016/j.febslet.2014.11.030. Epub 2014 Nov 29.

Abstract

ASPP2 is an important tumor suppressor protein promoting p53-dependent and-independent apoptosis. However, it has been unclear how ASPP2 protein is regulated. Here, we identified Itch as the E3 ubiquitin ligase for ASPP2. Itch interacts with ASPP2 and mediates its degradation and ubiquitination in vivo. The PPXY motif of ASPP2 interacts with the WW domains of Itch. Yap1 competes with Itch for binding to ASPP2, and prevents Itch-mediated degradation and ubiquitination of ASPP2. Together, these observations reveal that Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability through competing post-translational regulatory mechanism of ASPP2.

Keywords: Apoptosis; PPXY motif; Proteasomal degradation; Ubiquitination; WW domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Line
  • Humans
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Stability
  • Proteolysis*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription Factors
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination / physiology*
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Phosphoproteins
  • Repressor Proteins
  • TP53BP2 protein, human
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • ITCH protein, human
  • Ubiquitin-Protein Ligases