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'Shuttling' protein possibly key to resilience of cancer cells

n the Department of Biological Sciences; and Hu.

The research focuses on two proteins called c-Jun and ATF2, which are key components of a protein complex called activating protein-1, or AP-1. AP-1 is a major "transcription factor" that binds to DNA, activating the "expression" of genes required to produce proteins needed for vital cellular processes. The proteins that make up AP-1, including ATF2 and c-Jun, often join together in the nucleus, forming either "homodimers," when two of the same proteins join, or "heterodimers," when two different proteins come together.

"Current thinking is that all of these AP-1 proteins in healthy cells are localized, or confined, to the nucleus," Hu said. "But in this work we found for the first time that ATF2 constantly shuttles between the cytoplasm and the nucleus."

The researchers found that the ATF2 protein possesses "nuclear export" and "nuclear localization" signals, which enable it to travel out of and back into the nucleus, respectively. The researchers also discovered that if ATF2 attaches to c-Jun in the nucleus, forming a heterodimer, the nuclear export signal is blocked, preventing ATF2 from traveling from the nucleus to the cytoplasm.

Researchers had already known that chemotherapy and radiation cause cancer cells to increase production of ATF2. The Purdue researchers found that "overexpressed," or overproduced, ATF2 is predominantly located in the cytoplasm because of an inadequate amount of c-Jun in the nucleus, suggesting it is likely that overexpressed ATF2 also may be localized in the cytoplasm in cancer cells, Hu said.

The Purdue researchers not only discovered that ATF2 is localized in the cytoplasm of the mouse cancer stem cells, but also that exposing the cells to ultraviolet light induced more production of c-Jun protein in the nucleus, causing the ATF2 to bind with c-Jun, stopping the shuttling process and causing cell death. The c-Jun-ATF2 heterodimers cause more c-J
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Source:Purdue University


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