Gadd45a Orchestrates Much of Muscle Atrophy

An important regulatory gene for muscle atrophy is identified: "We now understand a key molecular mechanism of skeletal muscle atrophy. This finding could help us find a therapy for treating muscle atrophy in patients. ... The team has identified a single protein, called Gadd45a, and determined that it orchestrates 40 percent of the gene activity that ultimately causes skeletal muscle to atrophy. ... The researchers learned that Gadd45a affected muscles in two main ways: it instructed muscle cells to produce fewer proteins (needed to maintain muscle), and it caused proteins already existing in muscle fibers to break down. The result on both counts: muscle atrophy. The team then turned to find out how Gadd45a did its work. The nucleus of a muscle cell that is stressed changes from a cigar shape to a swollen bulb, with enlarged nucleoli (protein containers inside the nucleus). When Adams and his team injected Gadd45a into a muscle cell, the nucleus changed shape the same way as if it were stressed. ... To put this all together, it means Gadd45a is going into the muscle nucleus, and it totally changes it, so much so that the changes are visible. It's turning genes on, and it's turning genes off. It's changed the cell. ... Gadd45a changes roughly 600 genes associated with muscle atrophy, by increasing mRNAs charged either with breaking down muscle proteins or reducing muscle protein growth. ... Gadd45a is like a central switch for muscle atrophy. If you can block it, you can conceivably stunt muscle atrophy to a large extent."

Link: http://now.uiowa.edu/2012/08/researchers-identify-key-culprit-causing-muscle-atrophy

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