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Toronto researchers obtain detailed molecular 'signature' for Tankyrase
Date:12/8/2011

Toronto, ON -- The Samuel Lunenfeld Research Institute's Drs. Frank Sicheri, Tony Pawson and Sebastian Guettler, in collaboration with Dr. Robert Rottapel at the Ontario Cancer Institute, have uncovered the detailed architecture of a crucial component of Tankyrase, a protein linked to the bone development disorder cherubism and involved in a myriad of cellular processes. The discovery is the first structural insight into precisely how the enzyme correctly identifies its targets, or substrates. The work provides researchers with a greater understanding of Tankyrase's cellular control processes, and may also lead to the development of new designer drugs to treat cancer.

"Until now, we did not understand, from a structural perspective, how Tankyrase identifies its substrates," said Dr. Sicheri, Lunenfeld Senior Investigator and one of the lead authors of the study. "At atomic resolution, we now have a clearer picture of what these substrates may be, and have new insight into possible novel functions of Tankyrase."

The findings are available online today and will be published in the December 9 issue of the leading biomedical journal Cell.

Tankyrase is a poly(ADP-ribose)polymerase (PARP) -- one protein of a family of enzymes that modify other proteins with chains of ADP-ribose and affect many cellular processes. The modification reactions carried out by Tankyrase can directly alter some proteins' functions, bring proteins together in protein complexes, or can mark others for degradation.

Initially intrigued by Tankyrase because of its involvement in cherubism (a rare genetic disorder caused by mutations in the signaling protein 3BP2), the researchers built upon the findings of Dr. Rottapel's laboratory. This laboratory found that Tankyrase normally recognizes 3BP2 and targets it for destruction. The amino acids mutated in cherubism coincide with precisely the region in 3BP2 that is recognized by Tankyrase, or the "Tankyrase b
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Contact: Karin Fleming
fleming@lunenfeld.ca
416-586-4800 x2046
Samuel Lunenfeld Research Institute
Source:Eurekalert

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