Chemical genetics identify eIF2α kinase heme-regulated inhibitor as an anticancer target (original) (raw)

• Marshall, L., Kenneth, N.S. & White, R.J. Elevated tRNA(iMet) synthesis can drive cell proliferation and oncogenic transformation. Cell 133, 78–89 (2008).
  Article CAS Google Scholar
• Ranganathan, A.C., Ojha, S., Kourtidis, A., Conklin, D.S. & Aguirre-Ghiso, J.A. Dual function of pancreatic endoplasmic reticulum kinase in tumor cell growth arrest and survival. Cancer Res. 68, 3260–3268 (2008).
  Article CAS PubMed Central Google Scholar
• Harding, H.P. et al. Ppp1r15 gene knockout reveals an essential role for translation initiation factor 2 alpha (eIF2alpha) dephosphorylation in mammalian development. Proc. Natl. Acad. Sci. USA 106, 1832–1837 (2009).
  Article CAS Google Scholar
• Heaney, J.D., Michelson, M.V., Youngren, K.K., Lam, M.Y. & Nadeau, J.H. Deletion of eIF2beta suppresses testicular cancer incidence and causes recessive lethality in agouti-yellow mice. Hum. Mol. Genet. 18, 1395–1404 (2009).
  Article CAS PubMed Central Google Scholar
• Skalnikova, H. et al. Protein signaling pathways in differentiation of neural stem cells. Proteomics 8, 4547–4559 (2008).
  Article CAS Google Scholar
• Asano, K., Clayton, J., Shalev, A. & Hinnebusch, A.G. A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo. Genes Dev. 14, 2534–2546 (2000).
  Article CAS PubMed Central Google Scholar
• Algire, M.A., Maag, D. & Lorsch, J.R. Pi release from eIF2, not GTP hydrolysis, is the step controlled by start-site selection during eukaryotic translation initiation. Mol. Cell 20, 251–262 (2005).
  Article CAS Google Scholar
• Prostko, C.R., Dholakia, J.N., Brostrom, M.A. & Brostrom, C.O. Activation of the double-stranded RNA-regulated protein kinase by depletion of endoplasmic reticular calcium stores. J. Biol. Chem. 270, 6211–6215 (1995).
  Article CAS Google Scholar
• Srivastava, S.P., Davies, M.V. & Kaufman, R.J. Calcium depletion from the endoplasmic reticulum activates the double-stranded RNA-dependent protein kinase (PKR) to inhibit protein synthesis. J. Biol. Chem. 270, 16619–16624 (1995).
  Article CAS Google Scholar
• Aktas, H. et al. Depletion of intracellular Ca2+ stores, phosphorylation of eIF2alpha, and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole. Proc. Natl. Acad. Sci. USA 95, 8280–8285 (1998).
  Article CAS Google Scholar
• Donzé, O., Jagus, R., Koromilas, A.E., Hershey, J.W. & Sonenberg, N. Abrogation of translation initiation factor eIF-2 phosphorylation causes malignant transformation of NIH 3T3 cells. EMBO J. 14, 3828–3834 (1995).
  Article PubMed Central Google Scholar
• Rosenwald, I.B., Hutzler, M.J., Wang, S., Savas, L. & Fraire, A.E. Expression of eukaryotic translation initiation factors 4E and 2alpha is increased frequently in bronchioloalveolar but not in squamous cell carcinomas of the lung. Cancer 92, 2164–2171 (2001).
  Article CAS Google Scholar
• Abraham, N. et al. The murine PKR tumor suppressor gene is rearranged in a lymphocytic leukemia. Exp. Cell Res. 244, 394–404 (1998).
  Article CAS Google Scholar
• Rosenwald, I.B. et al. Expression of the translation initiation factors eIF-4E and eIF-2* is frequently increased in neoplastic cells of Hodgkin lymphoma. Hum. Pathol. 39, 910–916 (2008).
  Article CAS Google Scholar
• Rosenwald, I.B., Wang, S., Savas, L., Woda, B. & Pullman, J. Expression of translation initiation factor eIF-2alpha is increased in benign and malignant melanocytic and colonic epithelial neoplasms. Cancer 98, 1080–1088 (2003).
  Article CAS Google Scholar
• Wek, R.C., Jiang, H.Y. & Anthony, T.G. Coping with stress: eIF2 kinases and translational control. Biochem. Soc. Trans. 34, 7–11 (2006).
  Article CAS Google Scholar
• Chen, J.J. Regulation of protein synthesis by the heme-regulated eIF2alpha kinase: relevance to anemias. Blood 109, 2693–2699 (2007).
  CAS PubMed PubMed Central Google Scholar
• Chen, J.J. Heme-regulated elF-2a kinase. in Translational Control of Gene Expression (eds. Sonenberg, N. et al.) 529–546 (Cold Spring Harbor Laboratory Press, New York, 2000).
• Han, A.P., Fleming, M.D. & Chen, J.J. Heme-regulated eIF2alpha kinase modifies the phenotypic severity of murine models of erythropoietic protoporphyria and beta-thalassemia. J. Clin. Invest. 115, 1562–1570 (2005).
  Article CAS PubMed Central Google Scholar
• Harding, H.P., Zhang, Y., Bertolotti, A., Zeng, H. & Ron, D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol. Cell 5, 897–904 (2000).
  Article CAS Google Scholar
• Marbach, I., Licht, R., Frohnmeyer, H. & Engelberg, D. Gcn2 mediates Gcn4 activation in response to glucose stimulation or UV radiation not via GCN4 translation. J. Biol. Chem. 276, 16944–16951 (2001).
  Article CAS Google Scholar
• Su, Q. et al. Modulation of the eukaryotic initiation factor 2 alpha-subunit kinase PERK by tyrosine phosphorylation. J. Biol. Chem. 283, 469–475 (2008).
  Article CAS Google Scholar
• Biason-Lauber, A., Lang-Muritano, M., Vaccaro, T. & Schoenle, E.J. Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. Diabetes 51, 2301–2305 (2002).
  Article CAS Google Scholar
• Harding, H.P. et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 6, 1099–1108 (2000).
  Article CAS Google Scholar
• Lu, P.D., Harding, H.P. & Ron, D. Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response. J. Cell Biol. 167, 27–33 (2004).
  Article CAS PubMed Central Google Scholar
• Vattem, K.M. & Wek, R.C. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proc. Natl. Acad. Sci. USA 101, 11269–11274 (2004).
  Article CAS Google Scholar
• Ziegeler, G. et al. Embryonic lethal abnormal vision-like HuR-dependent mRNA stability regulates post-transcriptional expression of cyclin-dependent kinase inhibitor p27Kip1. J. Biol. Chem. 285, 15408–15419 (2010).
  Article CAS PubMed Central Google Scholar
• Brewer, J.W. & Diehl, J.A. PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc. Natl. Acad. Sci. USA 97, 12625–12630 (2000).
  Article CAS Google Scholar
• Lomenick, B. et al. Target identification using drug affinity responsive target stability (DARTS). Proc. Natl. Acad. Sci. USA 106, 21984–21989 (2009).
  Article CAS Google Scholar
• Moerke, N.J. et al. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 128, 257–267 (2007).
  Article CAS Google Scholar
• Lu, L., Han, A.P. & Chen, J.J. Translation initiation control by heme-regulated eukaryotic initiation factor 2alpha kinase in erythroid cells under cytoplasmic stresses. Mol. Cell. Biol. 21, 7971–7980 (2001).
  Article CAS PubMed Central Google Scholar
• Scheuner, D. et al. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol. Cell 7, 1165–1176 (2001).
  Article CAS Google Scholar
• Dever, T.E. Gene-specific regulation by general translation factors. Cell 108, 545–556 (2002).
  Article CAS Google Scholar
• Koromilas, A.E. et al. The interferon-inducible protein kinase PKR modulates the transcriptional activation of immunoglobulin kappa gene. J. Biol. Chem. 270, 25426–25434 (1995).
  Article CAS Google Scholar
• Boyce, M. et al. A pharmacoproteomic approach implicates eukaryotic elongation factor 2 kinase in ER stress-induced cell death. Cell Death Differ. 15, 589–599 (2008).
  Article CAS Google Scholar
• Boyce, M. et al. A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science 307, 935–939 (2005).
  Article CAS Google Scholar
• Harding, H.P. et al. Diabetes mellitus and exocrine pancreatic dysfunction in perk−/− mice reveals a role for translational control in secretory cell survival. Mol. Cell 7, 1153–1163 (2001).
  Article CAS Google Scholar
• Araki, E., Oyadomari, S. & Mori, M. Impact of endoplasmic reticulum stress pathway on pancreatic beta-cells and diabetes mellitus. Exp. Biol. Med. (Maywood) 228, 1213–1217 (2003).
  Article CAS Google Scholar
• Katayama, T. et al. Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response. Nat. Cell Biol. 1, 479–485 (1999).
  Article CAS Google Scholar
• Xu, C., Bailly-Maitre, B. & Reed, J.C. Endoplasmic reticulum stress: cell life and death decisions. J. Clin. Invest. 115, 2656–2664 (2005).
  Article CAS PubMed Central Google Scholar
• Palakurthi, S.S., Aktas, H., Grubissich, L.M., Mortensen, R.M. & Halperin, J.A. Anticancer effects of thiazolidinediones are independent of peroxisome proliferator-activated receptor gamma and mediated by inhibition of translation initiation. Cancer Res. 61, 6213–6218 (2001).
  CAS PubMed Google Scholar
• Aktas, H., Cai, H. & Cooper, G.M. Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27KIP1. Mol. Cell. Biol. 17, 3850–3857 (1997).
  Article CAS PubMed Central Google Scholar