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Study shows how retinoic acid enters a cell's nucleus

Cornell University researchers have revealed a process that has stumped scientists for many years: exactly how an acid derived from vitamin A enters a cell's nucleus, where it has strong anti-carcinogenic effects.

Discovery of this basic transport mechanism opens a new door for future research on related compounds. The finding has important implications for the fight against cancer and other diseases.

The research, which appears in a recent issue of the journal Molecular Cell (Vol. 18, No. 3), explains for the first time how the cancer-fighting vitamin A derivative retinoic acid (RA) gains entry into a cell's nucleus.

When vitamin A enters a cell's cytoplasm (the portion that lies between the outer membrane and the nucleus), it can be converted to RA, a member of a group of compounds that enter a cell's nucleus and play a role in triggering transcription. This is a basic process for relaying genetic information and switching genes on and off. In this role, RA can inhibit tumor growth. In fact, past clinical trials have shown that RA can help treat leukemia, head, neck and breast cancer. RA and its synthetic derivatives may also be useful in treatment of diabetes, arteriosclerosis and emphysema. Unfortunately, conventional treatments using RA require high, toxic doses, and tumors can develop resistance to the treatment.

Noa Noy, a professor of nutritional sciences at Cornell, and Richard Sessler, the paper's lead author and a graduate student in Noy's lab, wanted to learn how RA is transported into the cell's nucleus. The chemical structure of RA makes it hydrophobic, meaning it is barely soluble in water. But the path from the cell cytoplasm, where RA is made, to the nucleus requires passage through water, a difficult journey for a hydrophobic compound. For RA to rapidly enter a cell's nucleus, it must catch a ride on a water-soluble protein called cellular retinoic acid-binding protein type II (CRABP-II). This protein was discovered o
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Source:Cornell University News Service


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