Discovery of Protein's Doubly Protective Role Wins Research Prize

MD Anderson researchers followed a surprising clue to discover that a known cancer-fighting protein also limits the growth of cells damaged by reactive oxygen species, one type of the highly reactive molecules known as free radicals.

Their groundbreaking paper in the Proceedings of the National Academy of the Sciences won the Cozzarelli Prize Tuesday as the best paper in the Biological Sciences category published in the Proceedings during 2010. The prizes are given to the top paper in six categories out of more than 3,700 studies published by the journal each year.

Cheryl Walker's research team was studying one tumor-suppressing protein when they found another protective protein known to work inside the cell nucleus moonlighting in another part of the cell.

Following up on this surprise, they found the cancer-blocking nuclear protein ATM has a second job controlling and killing damaged cells out in the area between the nucleus and the cell membrane called the cytoplasm. ATM recognizes damage caused by reactive oxygen species and tells the injured cells to stop growing or orders them to devour themselves, a process called autophagy.

Elevated ROS has been linked to more than 150 diseases, including diabetes, cancer, neurodegenerative diseases and atherosclerosis. ATM is commonly mutated in cancer.

Previously, ATM was known to monitor DNA damage in the nucleus, halt cell division and order the cell to repair the damage. If repair fails, ATM sets off apoptosis -- programmed cell death.

"The Cozzarelli Prize is wonderful recognition of research that brought to light a brand new aspect of cell biology and marked a new direction for our lab," says Walker, a Ph.D. and professor in the Department of Molecular Carcinogenesis, located at MD Anderson's Virginia Harris Cockrell Cancer Research Center, Science Park, near Smithville, Texas.

"Discovery of ATM's additional anti-tumor role is the type of basic science research that heightens our understanding of cancer and paves the way for improved prevention and treatment," says Raymond DuBois, M.D., Ph.D., MD Anderson provost and executive vice president. "The Cozzarelli Prize is a great honor for Cheryl, her lab and MD Anderson.

"The award also highlights the opportunities available for graduate students at MD Anderson," DuBois says. Co-first author Angela Alexander is a doctoral student in The University of Texas Graduate School of Biomedical Sciences, which is operated jointly by MD Anderson and The University of Texas Health Science Center at Houston (UT Health).

The PNAS paper can be read here.

MD Anderson news release about the paper: Researchers Discover Second Protective Role for Tumor-Suppressor