TIEG1 induces apoptosis through mitochondrial apoptotic pathway and promotes apoptosis induced by homoharringtonine and velcade

FEBS Lett. 2007 Aug 7;581(20):3826-32. doi: 10.1016/j.febslet.2007.07.008. Epub 2007 Jul 16.

Abstract

Overexpression of TGFbeta inducible early gene (TIEG1) mimics TGFbeta action and induces apoptosis. In this study, we found that TIEG1 was significantly up-regulated during apoptosis induced by homoharringtonine or velcade. Overexpression of TIEG1 could induce apoptosis in K562 cells and promote apoptosis induced by HHT or velcade. TIEG1-induced apoptosis was shown to involve Bax and Bim up-regulation, Bcl-2 and Bcl-XL down-regulation, release of cytochrome c from mitochondria into the cytosol, activation of caspase 3 and disruption of the mitochondrial membrane potential (DeltaPsim). We concluded that TIEG1 is a key regulator which induces and promotes apoptosis through the mitochondrial apoptotic pathway.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Boronic Acids / toxicity*
  • Bortezomib
  • DNA-Binding Proteins / metabolism*
  • Early Growth Response Transcription Factors / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Harringtonines / toxicity*
  • Homoharringtonine
  • Humans
  • K562 Cells
  • Kruppel-Like Transcription Factors / metabolism*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mitochondria / metabolism*
  • Pyrazines / toxicity*
  • Transcription Factors / metabolism*

Substances

  • Boronic Acids
  • DNA-Binding Proteins
  • Early Growth Response Transcription Factors
  • Harringtonines
  • KLF10 protein, human
  • Kruppel-Like Transcription Factors
  • Pyrazines
  • Tieg1 protein, mouse
  • Transcription Factors
  • Bortezomib
  • Homoharringtonine