Tight Coordination of Protein Translation and Heat Shock Factor 1 Activation Supports the Anabolic Malignant State
Name
Amon_Tight coordination.pdf
Size
3.62 MB
Format
Adobe PDF
Checksum (MD5)
00e206947040a2f88e163daa0fe826d7
Author(s)
Santagata, S.
Mendillo, Marc L.
Subramanian, A.
Perley, C. C.
Roche, S. P.
Wong, B.
Narayan, Rajiv
Kwon, H.
Golub, Todd R.
Porco, J. A.
Alternative Title
Tight Coordination of Protein Translation and HSF1 Activation Supports the Anabolic Malignant State
Date Issued
July 2013
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Santagata, S., M. L. Mendillo, Y.-c. Tang, A. Subramanian, C. C. Perley, S. P. Roche, B. Wong, et al. “Tight Coordination of Protein Translation and HSF1 Activation Supports the Anabolic Malignant State.” Science 341, no. 6143 (July 18, 2013): 1238303–1238303.
Version
Author's final manuscript
Abstract
The ribosome is centrally situated to sense metabolic states, but whether its activity, in turn, coherently rewires transcriptional responses is unknown. Here, through integrated chemical-genetic analyses, we found that a dominant transcriptional effect of blocking protein translation in cancer cells was inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional regulator of the heat-shock response and many other cellular processes essential for anabolic metabolism, cellular proliferation, and tumorigenesis. These analyses linked translational flux to the regulation of HSF1 transcriptional activity and to the modulation of energy metabolism. Targeting this link with translation initiation inhibitors such as rocaglates deprived cancer cells of their energy and chaperone armamentarium and selectively impaired the proliferation of both malignant and premalignant cells with early-stage oncogenic lesions.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/science.1238303
