Co-ordinated downregulation of bcl-2 and bax expression during granulocytic and macrophage-like differentiation of the HL60 promyelocytic leukaemia cell line.
The bcl-2 protein suppresses apoptosis and the bax protein opposes the cytoprotective effect of bcl-2. A decrease in bcl-2 levels has been implicated in the induction of apoptosis during the terminal differentiation of HL60 myeloid leukaemia cells. We show here that bax protein also declined with a time course similar to the downregulation of bcl-2 following treatment of HL60 with phorbol myristate acetate (PMA), dimethyl sulphoxide (DMSO) or retinoic acid (RA). Decreased bcl-2 protein expression in induced cells was associated with down-regulation of its mRNA. By contrast, the decrease in bax occurred by a post-transcriptional mechanism. Co-ordinate downregulation of bcl-2 and bax proteins may fine-tune the induction of apoptosis during cellular differentiation.
Mengubas
K
K
Department of Haematology, Royal Free Hospital Medical School, London, UK.
Riordan
F A
FA
Hoffbrand
A V
AV
Wickremasinghe
R G
RG
D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D006098:Granulocytes / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics; D008264:Macrophages / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate