Phosphorylation of Nur77 by the MEK-ERK-RSK cascade induces mitochondrial translocation and apoptosis in T cells

Journal of Immunology

Volumn 183, Issue 5, 2009, Pages 3268-3277

  Wang, Aibo ^a   Rud, Jonathan ^a   Olson Jr , Chris M ^a   Anguita, Juan ^a   Osborne, Barbara A ^a  

^a UNIVERSITY OF MASSACHUSETTS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; NUCLEAR RECEPTOR NUR77; S6 KINASE; SERINE; DNA BINDING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE; STEROID RECEPTOR;

ANIMAL CELL; ANIMAL CELL CULTURE; APOPTOSIS; ARTICLE; CELL DEATH; CONTROLLED STUDY; ENZYME SUBSTRATE; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IN VITRO STUDY; MITOCHONDRION; MOUSE; NONHUMAN; NUCLEAR EXPORT SIGNAL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; T LYMPHOCYTE; ACTIVE TRANSPORT; ANIMAL; CELL CULTURE; CELL LINE; CYTOLOGY; ENZYMOLOGY; IMMUNOLOGY; INTRACELLULAR FLUID; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE;

ACTIVE TRANSPORT, CELL NUCLEUS; ANIMALS; APOPTOSIS; CELL LINE; CELLS, CULTURED; DNA-BINDING PROTEINS; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HUMANS; INTRACELLULAR FLUID; MAP KINASE KINASE KINASES; MAP KINASE SIGNALING SYSTEM; MICE; MICE, TRANSGENIC; MITOCHONDRIA; PHOSPHORYLATION; PROTEIN TRANSPORT; RECEPTORS, STEROID; RIBOSOMAL PROTEIN S6 KINASES; T-LYMPHOCYTES;

EID: 70349241753     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0900894     Document Type: Article

References (50)

1. Liu, Z. G., S. W. Smith, K. A. McLaughlin, L. M. Schwartz, and B. A. Osborne. 1994. Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene Nur77. Nature 367: 281-284.
2. Woronicz, J. D., B. Calnan, V. Ngo, and A. Winoto. 1994. Requirement for the orphan steroid receptor Nur77 in apoptosis of T-cell hybridomas. Nature 367: 277-281.
3. Cainan, B. J., S. Szychowski, F. K. Chan, D. Cado, and A. Winoto. 1995. A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selection. Immunity 3: 273-282.
4. Zhou, T., J Cheng, P. Yang, Z. Wang, C. Liu, X. Su, H. Bluethmann, and J. D. Mountz. 1996. Inhibition of Nur77/Nurr1 leads to inefficient clonal deletion of self-reactive T cells. J. Exp. Med. 183: 1879-1892.
5. Rajpal A., and A. Winto. 2003. Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor. EMBO J. 22: 6526-6536.
6. Cheng, L. E., F. K. Chan, D. Cado, and A. Winto. 1997. Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis. EMBO J 16: 1865-1875.
7. Lin, B., S. K. Kolluri, F. Lin, W. Liu, Y. Han, X. Cao, M. I. Dawson, J. C. Reed, and X. K. Zhang. 2004. Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell 116: 527-540.
8. Stasik, I., A. Rapak, W. Kalas, E. Ziolo, and L. Strzadala. 2007. Ionomycin-induced apoptosis of thymocytes is independent of Nur77 NBRE or NurRE binding, but is accompanied by Nur77 mitochondrial targeting. Biochim. Biophys. Acta 1773: 1483-1490.
9. Thompson, J., and A. Winoto. 2008. During negative selection, Nur77 family proteins translocate to mitochondria where they associate with Bcl-2 and expose its proapoptotic BH3 domain. J. Exp. Med. 205: 1029-1036.
10. Turjanski, A. G., J. P. Vaque, and J. S. Gutkind. 2007. MAP kinases and the control of nuclear events. Oncogene 26: 3240-3253.
11. Sugawara, T., T. Moriguchi, E. Nishida, and Y. Takahama. 1998. Differential roles of ERK and p38 MAP kinase pathways in positive and negative selection of T lymphocytes. Immunity 9: 565-574. (Pubitemid 28499207)
12. + thymocytes. J. Exp. Med. 188: 1817-1830.
13. Sabapathy, K., Y. Hu, T. Kallunki, M. Schreiber, J. P. David, W. Jochum, E. F. Wagner, and M. Karin. 1999. JNK2 is required for efficient T- cell activation and apoptosis but not for normal lymphocyte development. Curr. Biol. 9: 116-125.
14. McNeil, L. K., T. K. Starr, and K. A. Hogquist. 2005. A requirement for sustained ERK signaling during thymocyte positive selection in vivo. Proc. Natl. Acad. Sci. USA 102: 13574-13579.
15. Werlen, G., B. Hausmann, D. Naeher, and E. Palmer. 2003. Signaling life and death in the thymus: timing is everything. Science 299: 1859-1863.
16. Sohn, S. J., G. M. Lewis, and A. Winoto. 2008. Non-redundant function of the MEK5-ERK5 pathway in thymocyte apoptosis. EMBO J. 27: 1896-1906.
17. Woronicz, J. D., A. Lina, B. J. Calnan, S. Szychowski, L. Cheng, and A. Winoto. 1995. Regulation of the Nur77 orphan steroid receptor in activation-induced apoptosis. Mol. Cell Biol. 15: 6364-6376.
18. Fujii, Y., S. Matshuda, G. Takayama, and S. Koyasu. 2008. ERK5 is involved in TCR-induced apoptosis through modification of Nur77. Genes Cells 13: 411-419.
19. Ananieva, O., A. Macdonald, X. Wang, C. E. McCoy, J. McIlrath, C. Tournier, and J. S. C. Arthur. 2008. ERK5 regulation in naive T-cell activation and survival. Eur. J. Immunol. 38: 2534-2547.
20. + thymocytes. J. Immunol. 164: 2326-2337.
21. Mariathasan, S., S. S. Ho, A. Zakarian, and P. S. Ohashi. 2000. Degree of ERK activation influences both positive and negative thymocyte selection. Eur. J. Immunol. 30: 1060-1068.
22. Mariathasan, S., A. Zakarian, D. Bouchard, A. M. Michie, J. C. Zuniga-Pflucker, and P. S. Ohashi. 2001. Duration and strength of extracelllular signal-regulated kinase signals are altered during positive versus negative thymocytes selection. J. Immunol. 167: 4966-4973.
23. Slagsvold, H., A. Østvold, A. Fallgren, and R. E. Paulsen. 2002. Nuclear receptor and apoptosis initiator NGFI-B is a substrate for kinase ERK2. Biochem. Biophys. Res. Commun. 291: 1146-1150.
24. Wingate, A. D., D. G. Campbell, M. Peggie, and S. J. C. Arthur. 2006. Nur77 is phosphorylated in cells by RSK in response to mitogenic stimulation. Biochem. J. 393: 715-724.
25. Jeffries S., and A. J. Capobianco. 2000. Neoplastic transformation by Notch requires nuclear localization. Mol. Cell Biol. 20: 3928-3941.
26. 1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. Blood 113: 1689-1698.
27. Nomura, M., S. Shimuzu, T. Ito, M. Narita, H. Matsuda, and Y. Tsujimoto. 1999. Apoptotic cytosol facilitates Bax translocation to mitochondria that involves cytosolic factor regulated by Bcl-2. Cancer Res. 59: 5542-5548. (Pubitemid 29526471)
28. Li, H., S. K. Kolluri, J. Gu, M. I. Dawson, X. Cao, P. D. Hobbs, B. Lin, G. Chen, J. Lu, F. Lin, et al. 2000. Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science 289: 1159-1164.
29. Riccardi, C., and I. Nicoletti. 2006. Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat. Protocols 1: 1458-1461.
30. Jehn, B. M., W. Bielk, W. S. Pear, and B. A. Osborne. 1999. Protective effects of Notch-1 on TCR-induced apoptosis. J. Immunol. 162: 635-638.
31. + thymocytes and mature T cells regulate Nur77 distinctly in response to TCR stimulation. J. Immunol. 177: 6660-6666.
32. Fahrner, T. J., S. L. Carroll, and J. Milbrandt. 1990. The NGFI-B protein, an inducible member of the thyroid/steroid receptor family, is rapidly modified post-translatinaly. Mol. Cell Biol. 10: 6454-6459.
33. Hazel, T. G., R. Misra, I. Davis, M. E. Grenberg, and L. Lau. 1991. Nur77 is differentially modified in PC12 cells upon membrane deplorization and growth factor treatment. Mol. Cell Biol. 6: 3239-3246.
34. Katagiri, Y., K. Takeda, Z. X. Yu, V. J. Ferrans, K. Ozato, and G. Guroff. 2000. Modulation of retinoid signalling through NGF-induced nuclear export of NGFI-B. Nat. Cell Biol. 2: 435-440.
35. Han, Y.-H., X. Cao, B. Lin, F. Lin, S. K. Kolluri, J. Stebbins, J. C. Reed, M. I. Dawson, and X.-K. Zhang. 2006. Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt. Oncogene 25: 2974-2986.
36. Mody, N., J. Leitch, C. Armstrong, J. Dixon, and P. Cohen. 2001. Effects of MAP kinase cascade inhibitors on the MKK5/ERK5 pathway. FEBS Lett. 502: 21-24.
37. Leighton, I. A., K. N. Dalby, F. B. Caudwell, P. T. W. Cohen, and P. Cohen. 1995. Comparison of the specificities of p70 S6 kinase and MAPKAP kinase-1 identifies a relatively specific substrate for p70 S6 kinase: the N-terminal kinase domain of MAPKAP kinase-1 is essential for peptide phosphorylation. FEBS Lett. 375: 289-293.
38. Anjum, R., P. P. Roux, B. A. Ballif, S. P. Gygi, and J. Blenis. 2005. The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling. Curr. Biol. 15: 1762-1767.
39. Pekarsky, Y., C. Hallas, A. Palamarchuk, A. Koval, F. Bullrich, H. Hirata, R. Bichi, J. Letofsky, and C. M. Croce. 2001. Akt phosphorylates and regulates the orphan nuclear receptor Nur77. Proc. Natl. Acad. Sci. USA 98: 3690-3694.
40. Masuyama, N., K. Oishi, Y. Mori, T. Ueno, Y. Takahama, and Y. Gotoh. 2001. Akt inhibits the orphan nuclear receptor Nur77 and T-cell apoptosis. J. Biol. Chem. 276: 32799-32805.
41. Daniels, M. A., E. Teixeiro, J. Gill, B. Hausmann, D. Roubaty, K. Holmberg, G. Werlen, G. A. Hollander, N. Gascoigne, and E. Palmer. 2006. Thymic selection threshold defined by compartmentalization of Ras/MAPK signaling. Nature 444: 724-729.
42. Richards, S. A., V. C. Dreisbach, L. O. Murphy, and J. Blenis. 2001. Characterization of regulatory events associated with membrane targeting of p90 ribosomal S6 kinase 1. Mol. Cell Biol. 21: 7470-7480.
43. Anjum, R., and J. Blenis. 2008. The RSK family of kinases: emerging roles in cellular signaling. Nat. Rev. Mol. Cell Biol. 9: 747-758.
44. Davis, I. J., T. G. Hazel, R.-H. Chen, J. Blenis, and L. F. Lau. 1993. Functional domains and phosphorylation of orphan receptor Nur77. Mol. Endocrinol. 7: 953-964.
45. Fisher, T. L., and J. Blenis (1996) Evidence for two catalytically active kinase domains in pp90RSK. Mol. Cell Biol. 16: 1212-1219. (Pubitemid 26064460)
46. Swanson, K. D., L. K. Taylor, L. Huang, A. L. Burlinggame, G. Landreth. 1999. Transcription factor phosphorylation by pp90rsk2. J. Biol. Chem. 274: 3385-3395.
47. Bouillet, P., J. F. Purton, D. I. Godfrey, L. Zhang, L. Coultas, H. Puthalakath, M. Pellegrin, S. Cory, J. M. Adams, and A. Strasser. 2002. BH3-only Bcl-2 family member Bim is reqired for apoptosis of autoreactive thymocytes. Nature 415: 922-926.
48. Weih, F., R. P. Ryseck, L. Chen, and R. Bravo. 1996. Apoptosis of Nur77/N10 transgenic thymocytes involves the Fas/Fas ligand pathway. Proc. Natl. Acad. Sci. USA 93: 5533-5538.
49. Kolluri, S. K., X. Zhu, X. Zhou, B. Lin, Y. Chen, K. Sun, X. Tian, J. Town, A. C. Satterthwait, and X. K. Zhang. 2008. A short Nur77-derived peptide coverts Bcl-2 from a protector to a killer. Cancer Cell 14: 285-298.
50. Chen, J., W. Fiskus, K. Eaton, P. Fernandez, Y. Wang, R. Rao, P. Lee, R. Joshi, Y. Yang, R. Kolhe, et al. 2008. Co-treatment with Bcl-2 antagonist sensitizes cutaneous T cell lymphoma to lethal action of HDAC7-Nur77 based mechanism. Blood 113: 4038-4048.