Okadaic acid-induced apoptosis of HL60 leukemia cells is preceded by destabilization of bcl-2 mRNA and downregulation of bcl-2 protein.

We have studied the actions of the protein phosphatase inhibitor okadaic acid (OA) on the expression of bcl-2 in HL60 human leukemia cells. OA induced downregulation of bcl-2 mRNA and protein prior to the induction of apoptosis. Downregulation of bcl-2 mRNA levels did not result from actions of OA on the bcl-2 upstream negative response element. Nuclear run-off analyses confirmed that OA did not affect bcl-2 gene transcription. However, OA caused a rapid increase in the rate of degradation of bcl-2 mRNA. Therefore, OA induces down-regulation of bcl-2 expression via destabilization of its transcript. The constitutive action of an OA-sensitive protein phosphatase may therefore maintain HL60 cell survival by blocking bcl-2 mRNA degradation.