Apoptosis is associated with modifications of bcl-2 mRNA AU-binding proteins.
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.
Donnini
M
M
Department of Experimental Pathology and Oncology, University of Florence, Italy.
Lapucci
A
A
Papucci
L
L
Witort
E
E
Tempestini
A
A
Brewer
G
G
Bevilacqua
A
A
Nicolin
A
A
Capaccioli
S
S
Schiavone
N
N
D020413:3' Untranslated Regions / Q000378:metabolism; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D061945:Caspase Inhibitors; D005786:Gene Expression Regulation; D006207:Half-Life; D006801:Humans; D019169:Jurkat Cells; D011485:Protein Binding / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays
D020413:3' Untranslated Regions; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone