The genetic region called CDKN2A is disrupted in a large percentage of human cancers. It is also one of the strangest parts of the genome, encoding for two completely different proteins. In this week’s Nature (Vol. 413, No. 6851, 06 Sep 2001), researchers confirm that both of the genes lurking in this locus are tumour suppressors, and unpick their varying effects.
Which protein is made from CDKN2A depends on where in its sequence the cell’s machinery begins reading its DNA code. Some bacteria do this, but CDKN2A is the only gene of its kind in mammals. Even weirder, the proteins, although very different in structure and function, both play critical roles putting the brakes on cell division. How and why CDKN2A got this way is an evolutionary riddle.
The two proteins are called p16INK4a and p19ARF (CDKN2A is also known as INK4a/ARF). The latter is a strong tumour suppressor, but the role of p16INK4a, which is the more commonly mutated in human cancers, was unknown. Two groups, led by Anton Berns of the Netherlands Cancer Institute, Amsterdam, and Ronald DePinho, of the Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, report that knocking out the p16Ink4a gene in mice, leaving the p19 ARF gene intact, predisposes the animals to melanomas. (Deletion of p19ARF has a stronger effect.)
Berns’ group has recreated a mutation in the gene found in a hereditary form of human melanoma, giving us one of the best mouse models of this increasingly common disease.
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(C) Nature press release.
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