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    Ozz may offer clues on muscle diseases in kids

    Wizardry of Ozz

    Research conducted by St. Jude investigators may help uncover the genetic cause of certain muscle diseases that occur for unknown reasons in children.

    Alessandra d’Azzo, PhD, of the Genetics and Tumor Cell Biology Department leads a team that discovered that the organization and stability of growing muscles in both human and laboratory models is critically dependent on the ability of a protein called Ozz to direct the timely destruction of membrane-bound b-catenin, one of the key proteins that orchestrate this process. d’Azzo is senior author of a report on these findings that appears in the February issue of Developmental Cell.

    Ozz directs destruction of b-catenin by assembling an active ubiquitin ligase complex, Ozz-E3, which breaks down this pool of the protein in muscle cells.

    The researchers also discovered that the Ozz gene overlaps another gene, which codes for an enzyme called protective protein/cathepsin A or PPCA.This enzyme is a key player in a process that breaks down certain molecules in the cellular structure called the lysosome. In addition, the Ozz gene shares with the PPCA gene a genetic “on switch,” called a promoter, which controls the expression of either gene, depending on which direction the promoter acts.

    “Our finding of the close link between PPCA and Ozz genes might explain why some children with a severe neurodegenerative disease caused by mutation of PPCA also suffer from muscle disorders. We are now studying that possibility,” d’Azzo said.

    The St. Jude team findings indicate that the loss of Ozz function leads to a disruption of muscle formation. Thus, the discovery of the Ozz function during muscle remodeling and growth might help determine why certain muscle diseases occur in children.

    March 2004