p53, commonly called the tumor suppressor gene, has attracted several fancy names, some worthy of Hollywood. “Guardian of the genome” (Lane, 1992), “Death star” (Vousden, 2000), “Good and bad cop” (Sharpless and DePinho, 2002), “An acrobat in tumorigenesis” (Moll and Schramm, 1998), are a few of the names that have been attributed to the p53 gene, according to the p53 website. Quite often p53 is called a master switch.

Now, scientists at Karolinska Institute in Stockholm, Sweden have identified a great many more proteins that are under the control of p53 than were previously known. And they are proposing a new, musical metaphor.

“P53 can be likened to a conductor leading a cellular orchestra,” says Professor Klas Wiman, one of the scientists involved in the study. “Whereas we previously knew which instruments, or genes, make up the orchestra, we now have an idea of the music it plays, by which I mean the proteins that the genes express.”

Wiman and his team have compared how the total protein configuration differs between cells with normally functioning p53 and cells lacking the protein. They show that p53 affects the expression of at least 115 other proteins, only 55 of which have so far been identified.

“These proteins have an important part to play in cancer-related functions, such as apoptosis and metastasis, as well as in aging,” says Professor Wiman. “Many of the mechanisms were previously unknown, and in several cases we can see changes at a protein level only, and not at a gene level. We believe this information to be of value to the development of new therapies.”

p53 targets identified by protein expression profiling
Klas G. Wiman, et al. Department of Oncology–Pathology, Cancer Center Karolinska, Karolinska Institutet, SE-171 76 Stockholm.
PNAS | March 27, 2007 | vol. 104 | no. 13 | 5401-5406
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