LA JOLLA, CAWhen cells find themselves in a tight spot, the cell cycle regulator p21 halts the cell cycle, buying cells time to repair the damage, or if all else fails, to initiate programmed cell death. In contrast to other stress-induced genes, which dispense with the regular transcriptional entourage, p21Cip1 still requires SKIP, a transcription elongation factor that also helps with the editing of transcripts, to be expressed, found researchers at the Salk Institute for Biological Studies.
In the absence of SKIP, the expression of p21Cip1 is rapidly down-regulated, predisposing cells to undergo programmed cell death, especially when faced with DNA damage-inducing chemotherapeutic agents. Their findings, reported in the April 1, 2011 issue of Genes & Development, not only define a new step that controls programmed cell death in cancer cells, but also suggest new approaches to enhance the efficacy of chemotherapeutic drugs.
"Interestingly, SKIP levels decline in cells treated with flavopiridol, which is currently in clinical trials as an anticancer agent for leukemia, and as a combination therapy for solid tumors," says Katherine A. Jones, Ph.D., a professor in the Regulatory Biology Laboratory, who led the study. "Our findings might help explain why flavopiridol works so well in combination with other cytotoxic drugs. Loss of SKIP sensitizes cancer cells to the apoptotic effects of DNA damage-inducing anticancer drugs."
The DNA in our cells is under constant attack from reactive chemicals generated as by-products of cellular metabolism. In addition, it is assaulted by x-rays, ultraviolet radiation from the sun, and environmental carcinogens such as tobacco smoke. If a cell suffers non-repairable injury it activates a built-in "auto-destruct" mechanism, known as programmed cell death or apoptosis. It eliminates abnormal cells from the body before they can cause disease, including cancer.
As a first-responder, the t
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