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UNC researchers discover 'master regulator' role for little-known protein in cancer cells
Date:4/29/2014

CHAPEL HILL, N.C. Researchers in the UNC School of Medicine found that the protein DAZAP1 plays a key role in the regulation of many genes through a process known as alternative splicing, and when highly expressed in cancer cell line experiments, DAZAP1 was shown to inhibit several types of cancer cells from dividing and moving.

The discovery, published in the journal Nature Communications, marks the first time this little-known protein has been characterized in relation to cancer development and tumor growth.

"If you knock down DAZAP1, then most of the genes involved in specific cancer cell signaling, cell death, and DNA repair are affected," said Rajarshi Choudhury, PhD, a postdoctoral research associate in the department of pharmacology and first author of the study. "It's a domino effect. DAZAP1 seems to be a sort of master regulator."

The protein regulates how genes are spliced together before the genes produce the proteins that are involved in causing cancer cells to grow and divide. When there's a lot of DAZAP1, cancer cells cease proliferating. "We've seen this in six different types of human cancer cell lines in the lab," Choudhury said.

Its role as a master regulator is what makes DAZAP1 different from other proteins implicated in cancer and an exciting candidate for further research.

DAZAP1 is like a commanding officer; other proteins are like soldiers. Many cancer drugs target one of the soldier proteins that have already been expressed from a gene, have received marching orders from other proteins, and are well on their way to causing problems, such as metastasis. Potential cancer drugs that target such soldier proteins sometimes prove ineffective because in some cases cancer cells figure out how to circumvent those proteins and thus the drugs that target those proteins.

DAZAP1, though, is far up the chain of command. It helps organize the genes that will create those soldier proteins
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Contact: Mark Derewicz
mark.derewicz@unch.unc.edu
919-923-0959
University of North Carolina Health Care
Source:Eurekalert

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