Targeting p53 by PTD-mediated transduction

Trends Biotechnol. 2004 Sep;22(9):431-4. doi: 10.1016/j.tibtech.2004.07.002.

Abstract

p53 is a major target for tumor therapy. Attempts have been made to restore or enhance p53 activity in tumor cells, including overexpression of exogenous p53 and small molecules that can rescue mutant p53. Notably, p53 peptides corresponding to the p53 carboxyl terminus can trigger a p53 response in both wild-type or mutant p53-containing cells. The recent protein transduction domain (PTD)-mediated cell entry might solve the obstacle of efficient delivery of peptides or large molecular biological cargos into cells. PTD-mediated transfer through the cell membrane occurs through a kind of endocytosis, macropinocytosis. Destabilization of macropinocytosomes by the influenza virus hemagglutinin protein (HA2) helps the escape of the PTD-cargo from macropinocytosomes and therefore significantly enhances the functional impact of transduced cargo.

MeSH terms

  • Antineoplastic Agents / metabolism
  • Aza Compounds / pharmacology
  • Binding Sites / genetics
  • Biological Transport / drug effects
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Drug Carriers / metabolism
  • Gene Products, tat / chemistry
  • Gene Products, tat / genetics
  • Gene Products, tat / physiology
  • Genetic Therapy / methods
  • Hemagglutinins, Viral / genetics
  • Hemagglutinins, Viral / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism
  • Models, Biological
  • Mutation
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Peptides / genetics
  • Peptides / metabolism
  • Pinocytosis / drug effects
  • Pinocytosis / physiology*
  • Protein Conformation
  • Pyrimidines / pharmacology
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Aza Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Drug Carriers
  • Gene Products, tat
  • Hemagglutinins, Viral
  • Peptides
  • Pyrimidines
  • Tumor Suppressor Protein p53
  • Viral Proteins
  • hemagglutinin fusogenic peptide, influenza virus
  • retro-inverso-TATp53C' peptide
  • 2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one
  • CP 31398