p53: an anticancer protein’s chequered past and promising future

Michael Eisenstein in Nature:

When scientists first came across p53 in 1979, it was an intriguing but not Earth-shattering discovery. Six groups independently discovered a cellular protein with a molecular weight of roughly 53 kilodaltons — hence the name. It seemed that p53 was interacting with a tumour-inducing virus called simian virus 40, and researchers soon showed that healthy cells forced to express this newly cloned gene encoding p53 quickly became cancerous1.

But the truth was more complicated. As more researchers began to study p53, it became apparent that the tumour-causing versions of the gene were actually mutated. The unmutated, or wild-type, version of the gene, which was cloned from humans and mice in the 1980s, exerted the exact opposite effect: the gene acted as a potent inhibitor of tumorigenesis2. Scientists had even got its size wrong; p53’s true molecular weight is closer to 44 kilodaltons. In the three decades since researchers came to this realization, p53’s biological significance has become ever more apparent. The protein coordinates a wide range of essential cellular functions, and its evolutionary history dates back to some of the earliest multicellular life on Earth.

More here.