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Disorderly protein brings order to cell division

The secret to the ability of a molecule critical for cell division to throw off the protein yoke that restrains its activity is the yoke itselfa disorderly molecule that seems to have a mind of its own, say investigators at St. Jude Children's Research Hospital, Innsbruck Medical University (Austria) and Max Planck Institute (Martinsried, Germany).

The researchers showed that the disorderly protein yoke, called p27, participates in its own destruction by swinging the end of its long arm up into a key side pocket of the cell division molecule called CDK2. After the end of p27 slips into the pocket, CDK2 marks p27 for destruction by tagging it with a molecule called phosphate. The tag signals the cell's protein destruction machinery to dispose of p27, freeing CDK2 to trigger cell division.

The finding is important because it explains how CDK2 normally shrugs off p27. Once free of p27, CDK2 can participate in a specific step of cell division. The findings also explain how some abnormal enzymes cause this to occur prematurely, putting cell division into overdrivea state that produces cancer. A report on the work appears in the January 25 issue of the journal Cell.

The long p27 molecule drapes itself like an arm over the shoulders and down the side of CDK2, the researchers explained. The upper arm of p27 binds tightly to the shoulders of CDK2; as the arm drops over the shoulders, the "elbow" of p27 inserts itself into a side "pocket" of the molecule.

Meanwhile, the long, floppy forearm and hand of p27 hangs freely below CDK2. Initailly, this is where the story of p27 became puzzling: the part of p27 that CDK2 must tag is on the "hand" at the free end of the floppy arm, at a point called amino acid threonine 187 (T187). But CDK2 can tag T187 only when this part of p27 fits into the pocket of CDK2, where the elbow of p27 is already lodged.

"Previous studies produced conflicting evidence to explain how CDK2 dispose
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Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
26-Jan-2007


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