AUF1 Is a bcl-2 A + U-rich element-binding protein involved in bcl-2 mRNA destabilization during apoptosis

J Biol Chem. 2002 May 3;277(18):16139-46. doi: 10.1074/jbc.M201377200. Epub 2002 Feb 20.

Abstract

We previously identified a conserved A + U-rich element (ARE) in the 3'-untranslated region of bcl-2 mRNA. We have also recently demonstrated that the bcl-2 ARE interacts with a number of ARE-binding proteins (AUBPs) whose pattern changes during apoptosis in association with bcl-2 mRNA half-life reduction. Here we show that the AUBP AUF1 binds in vitro to bcl-2 mRNA. The results obtained in a yeast RNA three-hybrid system have demonstrated that the 1-257-amino acid portion of p37 AUF1 (conserved in all isoforms), containing the two RNA recognition motifs, also binds to the bcl-2 ARE in vivo. UVC irradiation-induced apoptosis results in an increase of AUF1. Inhibition of apoptosis by a general caspase inhibitor reduces this increase by 2-3-fold. These results indicate involvement of AUF1 in the ARE/AUBP-mediated modulation of bcl-2 mRNA decay during apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / physiology
  • Base Sequence
  • Binding Sites
  • Conserved Sequence
  • Gene Expression Regulation
  • Genes, bcl-2*
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D*
  • Humans
  • Jurkat Cells
  • Kinetics
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Transcription, Genetic*
  • Transfection

Substances

  • HNRNPD protein, human
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • Protein Isoforms
  • RNA, Messenger
  • RNA-Binding Proteins
  • Recombinant Proteins