BOSTON--February 24, 1998--Researchers at Harvard Medical School have identified four human genes that serve a critical role in cell division. The findings provide a new target for anticancer agents, which may result in fewer therapeutic side-effects.
Hongtao Yu, a postdoctoral fellow in the laboratory of Marc Kirschner, the Carl W. Walter professor of cell biology at Harvard Medical School, and his colleagues used frog (Xenopus) protein sequences as a guide to identify the remaining four human genes in the eight-unit anaphase-promoting complex (APC). The APC's critical role in cell division makes it a perfect target for the fight against cancer, in which cells escape regulation and divide uncontrollably. The findings are published in the February 20 Science.
APC proteins are activated as the cell progresses through mitosis, but as yet, Kirschner and Yu do not know exactly how they are regulated. However, uncertainty about APC's regulation does not diminish the potential of this multi-subunit complex for anticancer therapeutics. With its seminal role in mitosis, the APC seems to be a perfect site to halt cell division. Like the anticancer drug Taxol that also disrupts mitosis, the advantage with an APC inhibitor would be preferential delivery to rapidly dividing tumor cells. "A lot of normal cells are just not dividing at all," says Yu. These law-abiding noncancerous cells would be invisible to the APC inhibitor, avoiding dangerous side effects that plague many anticancer drugs. The APC complex provides "a whole new set of targets which don't function at all in non-dividing cells," says Kirschner.
For successful cell division -- when the cytoplasmic and genetic contents of a cell are faithfully reproduced in the daughter progeny -- two cycles must be synchronized. The DNA is replicated in one cycle, and the chromosomes divide during mitosis -- the second cycle.