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The good, the bad and the ugly: The many roles of c-JUN in cancer
Date:6/28/2011

The process of cell division is tightly regulated, as mistakes may lead to cancer. The so-called c-JUN protein has been fingered as causing tumors in both skin and liver. The group of Veronika Sexl at the University of Veterinary Medicine, Vienna, has now uncovered a surprising detail with the discovery an additional function of c-JUN's also prevents silencing of an important anti-tumor factor. The results have recently been published in the open-access journal Oncotarget.

The c-JUN protein was initially described in the late 1980s as the mammalian equivalent of a protein responsible for causing cancer in birds. Intense research in a number of labs has subsequently led to a basic understanding of how the protein works. c-JUN is a transcription factor that modifies (phosphorylates) key regulatory proteins in the cell, thereby activating or deactivating them and leading to unregulated cell division and hence cancer. It has also become clear that c-JUN acts not on its own but in conjunction with an array of further proteins that modulate its function.

Karoline Kollmann in the group of Veronika Sexl, now at the University of Veterinary Medicine, Vienna, recently discovered an additional activity of c-JUN. Together with her collaboration partners at the Medical University of Vienna and in Madrid, she showed that c-JUN can bind to the promoter of a kinase gene, known as Cdk6, thereby preventing the gene from being inactivated (by means of methylation). The result is increased activity of Cdk6, which further stimulates cell division. c-JUN only activates transcription of Cdk6 in cancer cells, where it makes the disease progress even faster. Kollmann's work was published in April in the journal Blood (2011, Vol. 117, pp. 4065-4075).

The surprising aspect of the discovery is that the "new" function of c-JUN is independent of the protein's normal activity. Kollmann has now added a further twist to the tail with the discov
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Contact: Veronika Sexl
veronika.sexl@vetmeduni.ac.at
43-125-077-2910
University of Veterinary Medicine -- Vienna
Source:Eurekalert

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