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

The expression of genes requiring finely tuned control is regulated by a po sttranscriptional mechanism involving mRNA A + U-rich elements (AREs) coope rating with ARE-binding proteins (AUBPs) in modulation of mRNA stability. W e reported previously that an ARE in the bcl-2 mRNA 3'-untranslated region (3'-UTR) had destabilizing activity and was involved in bcl-2 downregulatio n during apoptosis in vitro. Here we demonstrate that the bcl-2 ARE complex es with a number of specific AUBPs, whose pattern undergoes changes followi ng application of apoptotic stimuli. The caspase inhibitor Z-VAD-fmk strong ly 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 m RNA stability control. (C) 2001 Academic Press.