Uncovering the PKR pathways potential for treatment of tumors

Future Oncology

Volumn 6, Issue 5, 2010, Pages 643-645

  Mounir, Zineb ^a,b   Koromilas, Antonis E ^a,b  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY RNA; DOUBLE STRANDED RNA; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INITIATION FACTOR; INITIATION FACTOR 4E; INITIATION FACTOR F2ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PIK3CA PROTEIN; PROTEIN KINASE R; PROTEIN P53; STRESS ACTIVATED PROTEIN KINASE; UNCLASSIFIED DRUG;

APOPTOSIS; BREAST CANCER; CANCER INHIBITION; CANCER THERAPY; CELL CYCLE ARREST; COLON CANCER; DIMERIZATION; EDITORIAL; GLIOBLASTOMA; GROWTH INHIBITION; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS INHIBITION; RNA TRANSLATION; TRANSCRIPTION REGULATION; ANIMAL; ENZYMOLOGY; GENETICS; NEOPLASM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; EIF-2 KINASE; HUMANS; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 77952509193     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.10.45     Document Type: Editorial

References (26)

1. Holcik M, Sonenberg N: Translational control in stress and apoptosis. Nat. Rev. Mol. Cell Biol. 6, 318-327 (2005).
2. Holland EC, Sonenberg N, Pandolf PP et al.: Signaling control of mRNA translation in cancer pathogenesis. Oncogene 23, 3138-3144 (2004).
3. Sonenberg N, Hinnebusch AG: Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136, 731-745 (2009).
4. Jagus R, Joshi B, Barber GN: PKR, apoptosis and cancer. Int. J. Biochem. Cell Biol. 31, 123-138 (1999).
5. Wek RC, Jiang HY, Anthony TG: Coping with stress: eIF2 kinases and translational control. Biochem. Soc. Trans. 34, 7-11 (2006).
6. Dever TE: Gene-specific regulation by general translation factors. Cell 108, 545-556 (2002).
7. Cole JL: Activation of PKR: an open and shut case? Trends Biochem. Sci. 32, 57-62 (2007).
8. Su Q, Wang S, Baltzis D et al.: Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2α RNA-dependent protein kinase. Proc. Natl Acad. Sci. USA 103, 63-68 (2006).
9. Koromilas AE, Roy S, Barber GN et al.: Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase. Science 257, 1685-1689 (1992).
10. Meurs EF, Galabru J, Barber GN et al.: Tumor suppressor function of the interferoninduced double-stranded RNA-activated protein kinase. Proc. Natl Acad. Sci. USA 90, 232-236 (1993).
11. Donze O, Jagus R, Koromilas AE et al.: Abrogation of translation initiation factor eIF-2 phosphorylation causes malignant transformation of NIH 3T3 cells. EMBO J. 14, 3828-3834 (1995).
12. Mounir Z, Krishnamoorthy JL, Robertson GP et al.: Tumor suppression by PTEN requires the activation of the PKR-eIF2a phosphorylation pathway. Sci. Signal. 2, RA85 (2009).
13. Cuddihy AR, Wong AH, Tam NW et al.: The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro. Oncogene 18, 2690-2702 (1999).
14. Cuddihy AR, Li S, Tam NW et al.: Double-stranded-RNA-activated protein kinase PKR enhances transcriptional activation by tumor suppressor p53. Mol. Cell. Biol. 19, 2475-2484 (1999).
15. Balachandran S, Kim CN, Yeh WC et al.: Activation of the dsRNA-dependent protein kinase, PKR, induces apoptosis through FADD-mediated death signaling. EMBO J. 17, 6888-6902 (1998).
16. Donze O, Dostie J, Sonenberg N: Regulatable expression of the interferoninduced double-stranded RNA dependent protein kinase PKR induces apoptosis and Fas receptor expression. Virology 256, 322-329 (1999).
17. Kumar A, Haque J, Lacoste J et al.: Double-stranded RNA-dependent protein kinase activates transcription factor NF-kB by phosphorylating IkB. Proc. Natl Acad. Sci. USA 91, 6288-6292 (1994).
18. Ishii T, Kwon H, Hiscott J et al.: Activation of the IkB a kinase (IKK) complex by double-stranded RNA-binding defective and catalytic inactive mutants of the interferoninducible protein kinase PKR. Oncogene 20, 1900-1912 (2001).
19. Bonnet MC, Weil R, Dam E et al.: PKR stimulates NF-kB irrespective of its kinase function by interacting with the IkB kinase complex. Mol. Cell. Biol. 20, 4532-4542 (2000).
20. Chu WM, Ostertag D, Li ZW et al.: JNK2 and IKKb are required for activating the innate response to viral infection. Immunity 11, 721-731 (1999).
21. Shir A, Levitzki A: Inhibition of glioma growth by tumor-specific activation of double-stranded RNA-dependent protein kinase PKR. Nat. Biotechnol. 20, 895-900 (2002).
22. Hennessy BT, Smith DL, Ram PT et al.: Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug Discov. 4, 988-1004 (2005).
23. Kim SH, Forman AP, Mathews MB et al.: Human breast cancer cells contain elevated levels and activity of the protein kinase, PKR. Oncogene 19, 3086-3094 (2000).
24. Kim SH, Gunnery S, Choe JK et al.: Neoplastic progression in melanoma and colon cancer is associated with increased expression and activity of the interferoninducible protein kinase, PKR. Oncogene 21, 8741-8748 (2002).
25. Hu W, Hofstetter W, Wei X et al.: Double-stranded RNA-dependent protein kinase-dependent apoptosis induction by a novel small compound. J. Pharmacol. Exp. Ther. 328, 866-872 (2009).
26. Nanduri S, Carpick BW, Yang Y et al.: Structure of the double-stranded RNA-binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA-mediated activation. EMBO J. 17, 5458-5465 (1998).