MODE OF ACTION OF MYC ONCOGENE
The oncogene c-Myc regulates cell proliferation, growth and cell death in normal cells. New work by Martin Eilers and colleagues, Universitaet Marburg, Germany and Joan Massagué and colleagues, Sloan-Kettering Cancer Center, New York, published in the April 2001 issue of Nature Cell Biology (3:392-399 and 3:400-408) respectively shed light on how this regulation is controlled.
p15Ink4b is a cyclin-dependent kinase (Cdk) inhibitor which is rapidly activated by the growth factor TGFb. This contributes towards inhibition of the cell division cycle.
Eilers and colleagues showed that Miz-1, a Myc-associated transcription factor, induces p15Ink4b expression and hence leads to inhibition of cell cycle progression. Myc can forms a complex with Miz, which inhibits it’s activity and prevents the accumulation of p15Ink4b. They go onto show that Myc prevents Miz activating gene expression by interfering with the recruitment of p300 (a transcription co-activator) to Miz-1. Myc mutant proteins that cannot bind Miz are unable to inhibit p15Ink4b accumulation which eventually leads to cellular immortalisation. Also Massagué and colleagues showed that TGFb prevents Myc recruitment to Miz, and hence relieves the repression which Myc would usually place on Miz.
Potential targets for cancer therapy may be uncovered from these studies.
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(C) Nature Cell Biology press release.
Message posted by: Trevor M. D'Souza