Michael B. Kastan, MD, PhD

Control of p53 could have medical uses

St. Jude investigators have discovered a mechanism that controls a key protein linked to the cell’s response to stress. This finding holds promise for new ways to enhance cancer therapies or protect cells from dying after exposure to damaging chemicals.

The gene for this protein, called p53, is the most commonly mutated gene in human cancer; it plays a critical role in helping cells respond to stress that damages DNA.

Previously, the rise in the level of p53 in cells with damaged DNA was thought to be due to a decrease in the rate at which the p53 protein is broken down in the cell. The St. Jude study showed that there is also an increased level of p53 protein synthesis following DNA damage. A report on this work appears in the October 7 issue of the journal Cell.

The St. Jude team showed that competing proteins, ribosomal protein L26 (RPL26) and nucleolin, vie for control of the messenger RNA (mRNA) that codes for p53. They identified a region of the mRNA, called the 52′-untranslated region that serves as a control switch for this process. In undamaged cells, nucleolin binds to this region of p53 mRNA and suppresses synthesis. But after DNA damage, RPL26 binds to this region and increases the translation of the mRNA into the p53 protein.

 “The ability to increase p53 function in tumor cells could increase the effectiveness of radiation and chemotherapy in treating certain types of tumors,” said Michael Kastan, MD, PhD, Hematology-Oncology chair and the paper’s senior author. “On the other hand, these insights provide a potentially novel way to try to decrease levels of p53 so that we could protect cells in normal tissues from dying after exposure to toxins or oxidative damage.” 

Other St. Jude authors of the study include Masatoshi Takagi, MD, Phd; Michael Absalon, MD, PhD; and Kevin McLure, PhD, Hematology-Oncology.

 

Last update: November 2005

 


Email This Article Email This Article   |   Print Print