Repairing a cell’s cancer defenses

Repairing a cell’s cancer defenses looks possible now that scientists have determined how mutations prevent a tumor-suppressing protein from doing its job. In healthy cells, the protein p53 monitors the transcription of genetic information from DNA to RNA. When p53 detects DNA damage or incipient cancer, it blocks DNA replication and kills the cancer cells. Mutated p53, which turns up in half of all human cancers, is powerless to prevent errors from propagating and resulting tumor cells from proliferating. Now, Andreas Joerger, Hwee Ching Ang, and Alan Fersht of Cambridge University in England have used x-ray crystallography to identify structural changes caused by the mutations. Overall, a substantial fraction of the mutations don’t prevent p53 from folding or from binding to DNA. Rather, the mutations make the protein so floppy that it melts at body temperature and flubs its tumor-suppressing role. The finding gives the researchers hope that drugs could bind and buttress p53’s structure to restore its stability and health-preserving function. (A. C. Joerger, H. C. Ang, A. R. Fersht, Proc. Natl. Acad. Sci. USA 103 , 15056, 2006 http://dx.doi.org/10.1073/pnas.0607286103 .)