A TALE OF THREE PROTEINS
In mammalian cells, ‘Id’ proteins help control cell proliferation and differentiation, which can be important in tumour progression. Another protein, ‘Rb’, also helps restrict cell proliferation. The gene coding Rb is one of the most important tumour suppressor genes studied and normal Rb function is removed in just about all human tumours. A third protein, ‘Myc’, is a transcription factor also strongly implicated in driving cell proliferation — Myc activity runs amok in many cancers and can force cells to bypass the inhibitory Rb pathway.
This week (Nature, 05 Oct 2000, VOL. 407, NO. 6804), Antonio Iavarone and colleagues at the Albert Einstein College of Medicine, New York, report intriguing further connections between the three proteins. By investigating mice that cannot express ‘Id2’ or Rb, they found that, during the normal cell cycle, Rb stops Id acting on its usual targets. But when Myc is overexpressed, it subverts the Rb’s tumour suppression activity by directly activating the Id2 gene. This may have a key role in a very aggressive neuronal cancer called neuroblastoma.
The work, therefore, connects three proteins known to be involved in cancer, and helps show how they act together to derail the cell cycle, producing uncontrolled cell proliferation. Inhibiting Id2-protein activity in tumour cells that overexpress Myc could help restore Rb proliferation control, the researchers say.
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