St. Jude scientists have discovered another way the tumor suppressor protein p53 earns its title as guardian of the genome.
P53 is one of the most famous cancer-related molecules. Its job is to keep tumors from forming. The protein does that by prompting stressed or damaged cells to die or stop dividing. The protein or the pathway that controls p53 does not work properly in most cancers.
P53 is best known for working in the cell nucleus. But earlier research showed p53 also works outside the nucleus of cells to trigger cell death.
Now scientists have discovered how p53 achieves the latter task. The results also suggest how small molecules may be used in the future to trigger the same mechanism to help kill cancer cells.
“These results expand our understanding of how p53 regulates cell behavior and highlight a possible new way to make tumor cells easier to kill,” said Richard Kriwacki, PhD, of St. Jude Structural Biology.
The study appears in the journal Molecular Cell.
July 30, 2015
Follis AV, Llambi F, Merritt P, Chipuk JE, Green DR, Kriwacki RW. Pin1-Induced Proline Isomerization in Cytosolic p53 Mediates BAX Activation and Apoptosis. Mol Cell 59(4):677-84, 2015. doi: 10.1016/j.molcel.2015.06.029.