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Sensing Reduced Translation

Chemical and genetic screening links ribosome activity levels and a transcriptional regulator in malignant cells. The interplay between metabolic pathways and the cellular survival programs that enable tumors to grow are poorly understood. Heat shock factor 1 (HSF1) coordinates an unexpectedly diverse transcriptional network involved in oncogenesis. Santagata et al. (see the Perspective by Gandin and Topisirovic) found that reduced translation may be used to sense a cell’s metabolic status and regulate transcription, in particular by inactivating HSF1 with consequent affects on its targets. Small-molecule drugs that affected this link were able to inhibit the growth of transformed cells in culture and of an animal tumor model. S. Santagata, M. L. Mendillo, Y.-c. Tang, A. Subramanian, C. C. Perley, S. P. Roche, B. Wong, R. Narayan, H. Kwon, M. Koeva, A. Amon, T. R. Golub, J. A. Porco Jr., L. Whitesell, S. Lindquist, Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state. Science 341, 1238303 (2013). [Abstract] [Full Text] V. Gandin, I. Topisirovic, Trans-HSF1 express. Science 341, 242–243 (2013). [Abstract] [Full Text]