Inhibition of NF-kappa B by a cell permeable form of I kappa B alpha induces apoptosis in eosinophils

S Fujihara, E Jaffray, S N Farrow, A G Rossi, C Haslett, R T Hay

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

An 11 amino acid HIV-TAT peptide can deliver target proteins into a variety of cells in a receptor-independent manner. To generate a highly specific inhibitor of the transcription factor NF-kappaB, we have fused the TAT-peptide to a version of IkappaBalpha that is resistant to signal-induced degradation. TAT-IkappaBalpha(S32A, S36A) inhibited NF-kappaB-dependent transcription in HeLa and A549 cells by retaining NF-kappaB p65 in the cytoplasm. Introduction of TAT-IkappaBalpha(S32A, S36A) into human eosinophils inhibited the nuclear translocation of NF-kappaB and induced apoptosis. Thus, continuous NF-kappaB-dependent transcription is important for eosinophil survival. While eosinophils are normally refractive to standard methods of gene delivery, the ability of TAT fusion proteins to be taken up by these cells should enable a detailed molecular analysis of survival pathways in these cells. (C) 2004 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)632-637
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume326
DOIs
Publication statusPublished - 21 Jan 2005

Keywords

  • HIV-TAT
  • NF-kappa B
  • I kappa B alpha
  • TAT-I kappa B alpha
  • eosinophils
  • apoptosis
  • TAT FUSION PROTEINS
  • MAMMALIAN-CELLS
  • TRANSDUCTION
  • ACTIVATION
  • ASTHMA
  • DOMAIN
  • DEGRADATION
  • DELIVERY
  • BINDING
  • VITRO

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