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    Richard W. Kriwacki, PhD

    Collapse of protein bridge can cause disease

    The disruption of a molecular bridge that holds together the molecule p53 tends to destabilize this protein, allowing it to form potentially disease-causing aggregates, or “clumps,” according to a study by St. Jude investigators.

    The mutation that causes clumps to form is associated only with the pediatric cancer adrenocortical carcinoma (cancer of the outer layer of the adrenal gland), suggesting a link between clump formation for mutant p53 in adrenal cells and the resulting cancer.

    The finding suggests a link between p53 clumps and adrenocortical carcinoma, but mutations that disrupt various proteins have broader implications. The resulting aggregates, called amyloid fibrils, are associated with diseases such as Alzheimer’s and Parkinson’s.

    When p53 is mutated, the defective p53 proteins that are produced can’t trigger the feedback mechanism that normally controls their levels, according to Richard Kriwacki, PhD, Structural Biology.

    “The more defective p53 protein there is, the more chance there is for some of these proteins to become destabilized and form dysfunctional fibrils,” said Kriwacki, who is senior author of a report on this work that appears in the pre-publication issue of Protein Science.

    Other authors of the paper include Charles Galea, PhD, Structural Biology, who did much of the work on this project; and Prentice Bowman, a student at the University of Tennessee Health Science Center College of Medicine and former member of the St. Jude Pediatric Oncology Education Program and Rhodes College/St. Jude SummerPlus Program.

    St. Jude does both laboratory and clinical research in order to find cures for catastrophic diseases of children. Much of this research, especially in the laboratory, leads to discoveries of the basic workings of the body's cells. Therefore, some of our work has broader implications than childhood diseases and provides insights into adult diseases as well.

    Last update: January 2006