Cancer turns out to be a disease of protein aggregation

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Protein aggregation, generally with Alzheimer's disease and mad cows disease, is to play an important role in cancer. In a paper published in nature chemical biology, Frederic Rousseau and Joost Schymkowitz, both from the Vrije Universiteit Brussel, VIB and K.U.Leuven describe that certain mutations of p53, an important tumor suppressor cause the protein to misfold in a way that to start the proteins aggregate. This disrupts not only the protection function of normal p53, but also other related proteins.

p53 plays a central role in the protection against cancer

In the study of the p53 protein focused on, the a key role in protect the body from cancer plays. When p53 is usually works, it controls cell division. P53 control no longer - can for example, if there is a mutation in the protein - cells begin, in uncontrolled and a tumor lead sharing. Mutations in the p53 are in about half of the cases observed an important goal of the protein in the development of novel cancer therapies.

Mutated p53 aggregates

"We have revealed a new mechanism for the action of mutant p53," says Jie Xu of VIB and k.u Leuven. "Mutations in the p53 cause the protein to lose its protective function." The proteins in the form of change, hooks into each other and start to aggregate. "The active p53 disappears from the cell and can not more lead its supervisory function properly." The mechanism has occurred in about a third of p53 mutations.

Complete switch of the character

In addition, the p53 mutations lead to take a completely different character. As a protective factor is, changes the mutated p53 in a substance that accelerates in fact tumor growth. It seems to form aggregates with control substances (p63 and p73) in the cell, so that they also lose their function.

Other proteins underlying cancer and Alzheimer's disease

Even if the underlying principle - similar to occurs protein aggregation - in particular cancer, Alzheimer's disease and systemic amyloidosis, diseases are otherwise totally unconnected with each other. Cancer leads to the clustering of p53 protein uncontrolled cell growth. In Alzheimer's disease, the clustering of beta-amyloid protein leads off brain cells to die.

Financing

This research was by FWO, Chinese Science Council and financed VIB.

Scientific publicationJie Xu et al, strengthening the function of mutant p53 of Coaggregation with multiple tumor suppressors, nature chemical biology

Research-team

This study was of Jie Xu under the supervision of Frederic Rousseau en Joost Schymkowitz of the VIB, Vrije Universiteit Brussel en K.U.Leuven performed. Also, Jean-Christophe marine and Diether Lambrechts worked, at K.U.Leuven connected other VIB scientist, to the work.

Source:
VI
K.U.Leuven
Vrije Universiteit Brussel