Apoptosis is associated with modifications of bcl-2 mRNA AU-binding proteins

Biochem Biophys Res Commun. 2001 Oct 12;287(5):1063-9. doi: 10.1006/bbrc.2001.5700.

Abstract

The expression of genes requiring finely tuned control is regulated by a posttranscriptional mechanism involving mRNA A + U-rich elements (AREs) cooperating with ARE-binding proteins (AUBPs) in modulation of mRNA stability. We reported previously that an ARE in the bcl-2 mRNA 3'-untranslated region (3'-UTR) had destabilizing activity and was involved in bcl-2 downregulation during apoptosis in vitro. Here we demonstrate that the bcl-2 ARE complexes with a number of specific AUBPs, whose pattern undergoes changes following application of apoptotic stimuli. The caspase inhibitor Z-VAD-fmk strongly attenuates both bcl-2 mRNA decay and bcl-2 AUBP pattern changes elicited by apoptotic stimuli, indicating the involvement of bcl-2 AUBPs in bcl-2 mRNA stability control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / metabolism
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Apoptosis*
  • Caspase Inhibitors
  • Gene Expression Regulation
  • Half-Life
  • Humans
  • Jurkat Cells
  • Protein Binding / radiation effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • RNA Processing, Post-Transcriptional*
  • RNA Stability
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Ultraviolet Rays

Substances

  • 3' Untranslated Regions
  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • RNA-Binding Proteins
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone