cIAP-1, but not XIAP, is cleaved by caspases during the apoptosis induced by TGF-beta in fetal rat hepatocytes

FEBS Lett. 2002 Jun 5;520(1-3):93-6. doi: 10.1016/s0014-5793(02)02774-6.

Abstract

We have studied the expression of XIAP, cIAP-1 and cIAP-2 in fetal rat hepatocytes and its possible regulation by pro-apoptotic stimuli (transforming growth factor-beta (TGF-beta)) and survival signals (epidermal growth factor (EGF)). The three forms of inhibitor of apoptosis proteins (IAPs) are expressed in fetal hepatocytes and only cIAP-1, but not XIAP or cIAP-2, is cleaved during TGF-beta-induced apoptosis. The pan-caspase inhibitor Z-VAD.fmk blocked this effect, which indicates that cIAP-1 is a caspase substrate. EGF plays a dual role in the regulation of IAPs expression. On one hand, it increases cIAP-1 and cIAP-2 basal expression and, on the other hand, it blocks the cleavage of cIAP-1 by caspases induced by TGF-beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Caspase 3
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cells, Cultured
  • Cysteine Proteinase Inhibitors / metabolism*
  • DNA / drug effects
  • DNA / metabolism
  • Dose-Response Relationship, Drug
  • Fetus
  • Hepatocytes / cytology
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Time Factors
  • Transforming Growth Factor beta / pharmacology*
  • X-Linked Inhibitor of Apoptosis Protein

Substances

  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Proteins
  • Transforming Growth Factor beta
  • X-Linked Inhibitor of Apoptosis Protein
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • DNA
  • Casp3 protein, rat
  • Caspase 3
  • Caspases