In Brief

Abstract

A novel protein has been shown to put the brakes on cancer. Surprisingly, it is coded by the same gene that promotes cancer – the two proteins being splice alternatives of the same gene. STATs (signal transducers and activators of transcription) are a family of transcription activator proteins. Rockefeller University scientists have now shown that the only Drosophila gene locus for the STAT protein, the human counterpart of which is an oncogene, also codes for a second, shorter protein that is a negative regulator of the original STAT. This newly characterized shorter protein lacks the region responsible for activity in the longer form. The shorter STAT inhibits the original form by a dominant-negative mechanism, in which the full-length form cannot activate molecular targets owing to blockage and binding of the smaller inactive version. ‘In this post-genomic era, findings like this one make it more and more clear that alternate proteins, or protein isoforms, should be considered when attempting to explain complex biological phenomena,’ says James E. Darnell Jr, principal author of the report. Currently, the researchers are testing whether this same mechanism is conserved in humans. A STAT inhibitor would prove useful therapy for the ∼50% of human cancers in which STAT proteins are known to be overactive, including leukemia, breast, and head and neck cancer (Genes Dev. 16, 2379–89).