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

FEBS Letters

Riordan, Fiona A.¹  Foroni, Letizia¹  Hoffbrand, A.Victor¹  Mehta, Atul B.¹  Wickremasinghe, R.Gitendra¹ 

[1] Department of Hematology, Royal Free Hospital Medical School, Rowland Hill Street, London NW3 2PF, UK

关键词: Apoptosis;    Bcl-2;    Messenger RNA;    Leukemia;    Phosphoprotein phosphatase;    Okadaic acid;   

DOI  :  10.1016/S0014-5793(98)01070-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown