Alterations in the expression of various Bcl-2 family members may act as one means by which a cell's survival may be regulated. The mechanism by which cytokines regulate expression of Bcl-2 family members was examined in the haemopoietic cell line TF-1. Cytokine-induced Mcl-1 protein expression was shown to be controlled through a pathway dependent upon phosphatidylinositol 3-kinase (PI 3-kinase). The cytokine-induced increase in mRNA transcription was not dependent upon PI 3-kinase, thus dissociating the immediate-early transcription factors responsible for Mcl-1 transcription from the PI 3-kinase signalling pathway. In contrast, Mcl-1 mRNA levels were dependent upon MEK [mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated protein kinase kinase] activation, suggesting a role for the Ras/MEK/MAPK pathway in Mcl-1 transcription. Activation of PI 3-kinase was shown to be necessary to stimulate Mcl-1 protein translation. This was not due to any effect on prolonging the half-life of the protein. Finally, the lipid second messenger ceramide was shown to cause a reduction in Mcl-1 protein translation, probably via its ability to inhibit protein kinase B activation, providing further clues regarding the death-inducing effect of this lipid.
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June 2001
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Research Article|
May 24 2001
Distinct roles for extracellular-signal-regulated protein kinase (ERK) mitogen-activated protein kinases and phosphatidylinositol 3-kinase in the regulation of Mcl-1 synthesis
Kathryn M. SCHUBERT;
Kathryn M. SCHUBERT
Department of Medicine, University of British Columbia and Vancouver Hospital, Jack Bell Research Centre, 2660 Oak St. Vancouver, BC, Canada V6H 3Z6
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Vincent DURONIO
Vincent DURONIO
1
Department of Medicine, University of British Columbia and Vancouver Hospital, Jack Bell Research Centre, 2660 Oak St. Vancouver, BC, Canada V6H 3Z6
1To whom correspondence should be addressed (e-mail vduronio@interchange.ubc.ca).
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Publisher: Portland Press Ltd
Received:
December 08 2000
Revision Received:
February 23 2001
Accepted:
March 23 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 356 (2): 473–480.
Article history
Received:
December 08 2000
Revision Received:
February 23 2001
Accepted:
March 23 2001
Citation
Kathryn M. SCHUBERT, Vincent DURONIO; Distinct roles for extracellular-signal-regulated protein kinase (ERK) mitogen-activated protein kinases and phosphatidylinositol 3-kinase in the regulation of Mcl-1 synthesis. Biochem J 1 June 2001; 356 (2): 473–480. doi: https://doi.org/10.1042/bj3560473
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