Transcription Factor Is Key to Cell Survival
By Biotechdaily staff writers
Posted on 14 Oct 2002
A new study has defined the pivotal role of the Myc transcription factor in determining whether a cell with damage to its DNA will die (apoptosis) or will repair the damage and survive (cytostasis). The study was published October 2, 2002, in the online edition of Nature.Posted on 14 Oct 2002
Researchers at Memorial Sloan-Kettering Cancer Center (New York, NY, USA) working with colon cancer cells determined that cells containing a high level of the Myc protein cannot activate the production of the p21 gene, which inhibits cell division. Myc binds to p21 via the DNA-binding protein Miz-1. This interaction blocks p21 induction by p53 and other activators. As a result Myc switches, from cytostatic to apoptotic, the p53-dependent response of colon cancer cells to DNA damage. Myc does not modify the ability of p53 to bind to the p21or PUMA promoters, but selectively inhibits bound p53 from activating p21 transcription.
"Our work reveals a way we might coax cells to favor apoptosis instead of cytostasis in order to increase the effectiveness of chemotherapy,” said senior author Dr. Joan Massagué, chairman of the cell biology program at Memorial Sloan-Kettering. "Now, time and more research need to reveal how feasible this strategy would be in the clinic.”
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Memorial Sloan-Kettering Cancer Center
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