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

• Published in: FEBS letters Vol. 435; no. 2; pp. 195 - 198
• Main Authors: Riordan, Fiona A., Foroni, Letizia, Hoffbrand, A.Victor, Mehta, Atul B., Wickremasinghe, R.Gitendra
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 18.09.1998
• Subjects: Apoptosis; Apoptosis - drug effects; Bcl-2; Down-Regulation; Enzyme Inhibitors - pharmacology; HL-60 Cells; Humans; Leukemia; Messenger RNA; Okadaic acid; Okadaic Acid - pharmacology; Phosphoprotein phosphatase; Phosphoprotein Phosphatases - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; RNA, Messenger - biosynthesis; Bcl-2; Okadaic acid; Messenger RNA; Phosphoprotein phosphatase; Leukemia; Apoptosis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01070-9

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 downregulation 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.