Mechanism Allows Healthy Cells to Maintain Control of Cell Death Proteins

When normal cells suffer slight DNA damage, they block degradation of HIPK2 by Siah-1 for a short time. When the damage is repaired, the cell immediately resumes HIPK2 degradation. Only in severely damaged cells, such as those with a broken DNA double strand, is Siah-1 degradation of HIPK2 blocked permanently. As a result, HIPK2 accumulates, apoptosis is triggered, and the cell dies.

In some types of cancer cells this mechanism fails to operate. The degradation of HIPK2 by Siah-1 is not inhibited, and cells with damaged DNA proliferate instead of dying.

"Cancer medicine might be able to make use of our discovery,” said senior author Dr. Thomas G. Hofmann, a researcher at the German Cancer Research Center. "For example, we could use a Siah-1 blocker simultaneously with chemotherapy or radiotherapy to get the cells back into the apoptosis program.”


Related Links:
German Cancer Research Center