A conserved AU-rich element in the 3′ untranslated region of bcl-2 mRNA is endowed with a destabilizing function that is involved in bcl-2 down-regulation during apoptosis

摘要: The control of mRNA stability is becoming recognized as a crucial point gene expression regulation. A common element responsible for decay modulation the adenine- and uracil-rich that found in 3' untranslated region numerous mRNAs subjected to fast changes response various stimuli. Previously we identified post-transcriptional regulation level antiapoptotic bcl-2 gene, which could be involved t(14;18) lymphoma-associated overexpression. Here demonstrate endowed with an (ARE) characterized by high evolutionary conservation not only among all chordates examined, but even between nematode Caenorhabditis elegans (ced-9 gene). As other well-established destabilizing AREs, insertion ARE downstream from stable beta-globin causes enhanced transcript, proves its functional role. This possibility corroborated fact pathway leading modulating activity influenced PKC, since addition DAG TPA markedly attenuated potential. Conversely, it noteworthy when C(2)-ceramide added culture medium apoptotic agent, transcript harboring undergoes dramatic increase decay. observation clearly indicates function stimuli suggests this mechanism down-regulation during apoptosis. half-life Jurkat cells prolonged PKC stimulation shortened addition, strongly supporting view plays physiological role expression, particularly Thus, becomes new candidate mediating those changes-from apoptosis-associated tumor-associated overexpression-observed thus far profoundly influence single cell fate tissue homeostasis.