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A chaperone for the 'guardian of the genome'
Date:9/7/2011

Every cell has thousands of proteins whose activity and lifetime must be regulated to control the cellular life cycle from cell division to cell death. The heat shock protein Hsp90 plays a key role in this process. It is a so-called chaperone, a quality controller, as it were. It monitors and controls the quality and activity of many important signal proteins and helps them take on the right form. When the cell is exposed to high stress levels from heat or a lack of oxygen, Hsp90 is produced in larger quantities to shield its partner proteins from damage.

One of the most important partner proteins of Hsp90 is the tumor suppressor protein p53. It prevents the development of cancer at a number of points in the cell and is thus aptly referred to as the "guardian of the genome". When a cell's DNA becomes damaged, p53 ensures that the cell no longer divides and activates repair mechanisms. When too much genetic damage accumulates, the protein initiates a controlled cellular "suicide". When p53 is inactive, the cell continues to divide in spite of the damage and a tumor develops. In over half of all tumors the p53 protein is damaged or inactivated, meaning the control function cannot be carried out.

Hsp90, on the other had, binds to p53 and keeps it in a functional state until it can fulfill its actual purpose: Binding to specific DNA elements. However, exactly how and where the binding of p53 to Hsp90 takes place was hitherto neither clear nor had it been structurally characterized.

At the Department of Chemistry of the TU Muenchen, a team of biochemists headed by Professor Horst Kessler, in collaboration with the group of Professor Johannes Bucher, Chair of the Department of Biotechnology, has now succeeded in working out the details of how p53 binds to Hsp90. Horst Kessler was Chair of the Department of Organic Chemistry and Biochemistry at the TU Muenchen from 1989 to 2008 and has been Carl von Linde Professor at the Institute for Adva
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Contact: Dr. Markus Bernards
bernards@zv.tum.de
0049-892-892-2562
Technische Universitaet Muenchen
Source:Eurekalert

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