Proteolysis targeting peptide (PROTAP) strategy for protein ubiquitination and degradation

Biochem Biophys Res Commun. 2016 Feb 19;470(4):936-40. doi: 10.1016/j.bbrc.2016.01.158. Epub 2016 Jan 28.

Abstract

Ubiquitination proteasome pathway (UPP) is the most important and selective way to degrade proteins in vivo. Here, a novel proteolysis targeting peptide (PROTAP) strategy, composed of a target protein binding peptide, a linker and a ubiquitin E3 ligase recognition peptide, was designed to recruit both target protein and E3 ligase and then induce polyubiquitination and degradation of the target protein through UPP. In our study, the PROTAP strategy was proved to be a general method with high specificity using Bcl-xL protein as model target in vitro and in cells, which indicates that the strategy has great potential for in vivo application.

Keywords: Bcl-xL; PROTAP; Proteasome; Proteolysis; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • HEK293 Cells
  • Humans
  • Peptides / chemistry
  • Peptides / metabolism*
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding
  • Protein Engineering / methods
  • Proteolysis
  • Ubiquitin-Protein Ligases / chemistry*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitinated Proteins / chemistry*
  • Ubiquitinated Proteins / genetics
  • Ubiquitinated Proteins / metabolism*
  • Ubiquitination / physiology*

Substances

  • Peptides
  • Ubiquitinated Proteins
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex