Dr. Anthony E. Oro and colleagues (Stanford University) have identified two key Gli protein degradation signals that directly affect tumor latency in a mouse model of human skin cancer.
Their paper has been made available online ahead of print and will appear on the cover of the February 1 issue of the scientific journal Genes & Development.
Gli proteins are transcriptional mediators of the Sonic Hedgehog intracellular signaling pathway. Aberrant Shh signaling is implicated in a variety of human birth defects and about 25% of human tumors. Dr. Oro and colleagues found two sequences in the Gli1 protein – called Dn and Dc – that are recognized by the proteasome and facilitate Gli protein destruction. Mutations in these sequences (or "degrons" as they are called) prevent Gli1 degradation, causing, rather, the Gli1 protein to accumulate, and lead to accelerated tumorigenesis.
Heather Cosel | EurekAlert!
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