Akt-mediated phosphorylation increases the binding affinity of hTERT for importin α to promote nuclear translocation

Journal of Cell Science

Volumn 128, Issue 12, 2015, Pages 2287-2301

  Jeong, Sun Ah ^a   Kim, Kuglae ^a   Lee, Ji Hoon ^a   Cha, Jeong Seok ^a   Khadka, Prabhat ^a   Cho, Hyun Soo ^a   Chung, In Kwon ^a  

^a Yonsei University   (South Korea)

Author keywords

Akt; Importin receptor; Nuclear localization signal; Phosphorylation; Telomerase reverse transcriptase

Indexed keywords

KARYOPHERIN ALPHA; KARYOPHERIN BETA; PROTEIN KINASE B; TELOMERASE REVERSE TRANSCRIPTASE; KARYOPHERIN ALPHA 2; MESSENGER RNA; MUTANT PROTEIN; NUCLEAR LOCALIZATION SIGNAL; PHOSPHOSERINE; TELOMERASE; TERT PROTEIN, HUMAN;

ARTICLE; BINDING AFFINITY; BINDING SITE; CONTROLLED STUDY; CRYSTALLOGRAPHY; ENZYME ACTIVITY; HUMAN; HUMAN CELL; NUCLEAR IMPORT; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; ACTIVE TRANSPORT; AMINO ACID SEQUENCE; CELL NUCLEUS; CHEMISTRY; FLUORESCENT ANTIBODY TECHNIQUE; GENETICS; MCF 7 CELL LINE; METABOLISM; MOLECULAR GENETICS; MUTATION; NEOPLASM; PATHOLOGY; PHOSPHORYLATION; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SEQUENCE HOMOLOGY; STRUCTURE ACTIVITY RELATION; TUMOR CELL CULTURE; WESTERN BLOTTING;

ACTIVE TRANSPORT, CELL NUCLEUS; ALPHA KARYOPHERINS; AMINO ACID SEQUENCE; BLOTTING, WESTERN; CELL NUCLEUS; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; MCF-7 CELLS; MOLECULAR SEQUENCE DATA; MUTANT PROTEINS; MUTATION; NEOPLASMS; NUCLEAR LOCALIZATION SIGNALS; PHOSPHORYLATION; PHOSPHOSERINE; PROTO-ONCOGENE PROTEINS C-AKT; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; SEQUENCE HOMOLOGY, AMINO ACID; STRUCTURE-ACTIVITY RELATIONSHIP; TELOMERASE; TUMOR CELLS, CULTURED;

EID: 84932150036     PISSN: 00219533     EISSN: 14779137     Source Type: Journal    
DOI: 10.1242/jcs.166132     Document Type: Article

References (56)

1. Autexier, C. and Lue, N. F. (2006). The structure and function of telomerase reverse transcriptase. Annu. Rev. Biochem. 75, 493-517.
2. Bianchi, A. and Shore, D. (2008). How telomerase reaches its end: mechanism of telomerase regulation by the telomeric complex. Mol. Cell 31, 153-165.
3. Blackburn, E. H. (2001). Switching and signaling at the telomere. Cell 106, 661-673.
4. Chook, Y. M. and Süel, K. E. (2011). Nuclear import by karyopherin-betas: recognition and inhibition. Biochim. Biophys. Acta 1813, 1593-1606.
5. Chung, J., Khadka, P. and Chung, I. K. (2012). Nuclear import of hTERT requires a bipartite nuclear localization signal and Akt-mediated phosphorylation. J. Cell Sci. 125, 2684-2697.
6. Cingolani, G., Petosa, C., Weis, K. and Muller, C.W. (1999). Structure of importinbeta bound to the IBB domain of importin-alpha. Nature 399, 221-229.
7. Cingolani, G., Bednenko, J., Gillespie, M. T. and Gerace, L. (2002). Molecular basis for the recognition of a nonclassical nuclear localization signal by importin beta. Mol. Cell 10, 1345-1353.
8. Cong, Y.-S., Wright, W. E. and Shay, J. W. (2002). Human telomerase and its regulation. Microbiol. Mol. Biol. Rev. 66, 407-425.
9. Conti, E. and Kuriyan, J. (2000). Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. Structure 8, 329-338.
10. Conti, E., Uy, M., Leighton, L., Blobel, G. and Kuriyan, J. (1998). Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin alpha. Cell 94, 193-204.
11. de Lange, T. (2005). Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 19, 2100-2110.
12. Dickmanns, A., Bischoff, F. R., Marshallsay, C., Lührmann, R., Ponstingl, H. and Fanning, E. (1996). The thermolability of nuclear protein import in tsBN2 cells is suppressed by microinjected Ran-GTP or Ran-GDP, but not by RanQ69L or RanT24N. J. Cell Sci. 109, 1449-1457.
13. Emsley, P. and Cowtan, K. (2004). Coot: model-building tools for molecular graphics. Acta Crystallogr. D. Biol. Crystallogr. 60, 2126-2132.
14. Fontes, M. R. M., Teh, T. and Kobe, B. (2000). Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importinalpha. J. Mol. Biol. 297, 1183-1194.
15. Fontes, M. R. M., Teh, T., Jans, D., Brinkworth, R. I. and Kobe, B. (2003). Structural basis for the specificity of bipartite nuclear localization sequence binding by importin-alpha. J. Biol. Chem. 278, 27981-27987.
16. Forsythe, H. L., Jarvis, J. L., Turner, J. W., Elmore, L. W. and Holt, S. E. (2001). Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J. Biol. Chem. 276, 15571-15574.
17. Forwood, J. K., Lonhienne, T. G., Marfori, M., Robin, G., Meng, W., Guncar, G., Liu, S. M., Stewart, M., Carroll, B. J. and Kobe, B. (2008). Kap95p binding induces the switch loops of RanGDP to adopt the GTP-bound conformation: implications for nuclear import complex assembly dynamics. J. Mol. Biol. 383, 772-782.
18. Frohnert, C., Hutten, S., Wälde, S., Nath, A. and Kehlenbach, R. H. (2014). Importin 7 and Nup358 promote nuclear import of the protein component of human telomerase. PLoS ONE 9, e88887.
19. Griffith, J. D., Comeau, L., Rosenfield, S., Stansel, R. M., Bianchi, A., Moss, H. and de Lange, T. (1999). Mammalian telomeres end in a large duplex loop. Cell 97, 503-514.
20. Harreman, M. T., Hodel, M. R., Fanara, P., Hodel, A. E. and Corbett, A. H. (2003). The auto-inhibitory function of importin alpha is essential in vivo. J. Biol. Chem. 278, 5854-5863.
21. Holt, S. E., Aisner, D. L., Baur, J., Tesmer, V. M., Dy, M., Ouellette, M., Trager, J. B., Morin, G. B., Toft, D. O., Shay, J. W. et al. (1999). Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev. 13, 817-826.
22. Hübner, S., Xiao, C.-Y. and Jans, D. A. (1997). The protein kinase CK2 site (Ser111/112) enhances recognition of the simian virus 40 large T-antigen nuclear localization sequence by importin. J. Biol. Chem. 272, 17191-17195.
23. Jakel, S. and Gorlich, D. (1998). Importin beta, transportin, RanBP5 and RanBP7 mediate nuclear import of ribosomal proteins in mammalian cells. EMBO J. 17, 4491-4502.
24. Kang, S. S., Kwon, T., Kwon, D. Y. and Do, S. I. (1999). Akt protein kinase enhances human telomerase activity through phosphorylation of telomerase reverse transcriptase subunit. J. Biol. Chem. 274, 13085-13090.
25. Kann, M., Sodeik, B., Vlachou, A., Gerlich, W. H. and Helenius, A. (1999). Phosphorylation-dependent binding of hepatitis B virus core particles to the nuclear pore complex. J. Cell Biol. 145, 45-55.
26. Kelley, J. B., Talley, A. M. Spencer, A., Gioeli, D. and Paschal, B. M. (2010). Karyopherin a7 (KPNA7), a divergent member of the importin a family of nuclear import receptors. BMC Cell Biol. 11, 63.
27. Kim, N. W. and Wu, F. (1997). Advances in quantification and characterization of telomerase activity by the telomeric repeat amplification protocol (TRAP). Nucleic Acids Res. 25, 2595-2597.
28. Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L., Coviello, G. M., Wright, W. E., Weinrich, S. L. and Shay, J. W. (1994). Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011-2015.
29. Kim, J. H., Park, S.-M., Kang, M. R., Oh, S.-Y., Lee, T. H., Muller, M. T. and Chung, I. K. (2005). Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT. Genes Dev. 19, 776-781.
30. Kitamura, R., Sekimoto, T., Ito, S., Harada, S., Yamagata, H., Masai, H., Yoneda, Y. and Yanagi, K. (2006). Nuclear import of Epstein-Barr virus nuclear antigen 1 mediated by NPI-1 (Importin alpha5) is up-and down-regulated by phosphorylation of the nuclear localization signal for which Lys379 and Arg380 are essential. J. Virol. 80, 1979-1991.
31. Kobe, B. (1999). Autoinhibition by an internal nuclear localization signal revealed by the crystal structure of mammalian importin alpha. Nat. Struct. Biol. 6, 388-397.
32. Lange, A., Mills, R. E., Lange, C. J., Stewart, M., Devine, S. E. and Corbett, A. H. (2007). Classical nuclear localization signals: definition, function, and interaction with importin alpha. J. Biol. Chem. 282, 5101-5105.
33. Lee, G. E., Yu, E. Y., Cho, C. H., Lee, J., Muller, M. T. and Chung, I. K. (2004). DNA-protein kinase catalytic subunit-interacting protein KIP binds telomerase by interacting with human telomerase reverse transcriptase. J. Biol. Chem. 279, 34750-34755.
34. Lee, J. H., Khadka, P., Baek, S. H. and Chung, I. K. (2010). CHIP promotes human telomerase reverse transcriptase degradation and negatively regulates telomerase activity. J. Biol. Chem. 285, 42033-42045.
35. Lee, J. H., Lee, Y. S., Jeong, S. A., Khadka, P., Roth, J. and Chung, I. K. (2014). Catalytically active telomerase holoenzyme is assembled in the dense fibrillar component of the nucleolus during S phase. Histochem. Cell Biol. 141, 137-152.
36. Lingner, J., Cooper, J. P. and Cech, T. R. (1995). Telomerase and DNA end replication: no longer a lagging strand problem? Science 269, 1533-1534.
37. Lonhienne, T. G., Forwood, J. K., Marfori, M., Robin, G., Kobe, B. and Carroll, B. J. (2009). Importin-beta is a GDP-to-GTP exchange factor of Ran: implications for the mechanism of nuclear import. J. Biol. Chem. 284, 22549-22558.
38. Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S. and Olson, A. J. (2009). AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30, 2785-2791.
39. Muhlhausser, P., Muller, E.-C., Otto, A. and Kutay, U. (2001). Multiple pathways contribute to nuclear import of core histones. EMBO Rep. 2, 690-696.
40. Nakamura, T. M. and Cech, T. R. (1998). Reversing time: origin of telomerase. Cell 92, 587-590.
41. Nardozzi, J. D., Lott, K. and Cingolani, G. (2010). Phosphorylation meets nuclear import: a review. Cell Commun. Signal. 8, 32.
42. Oh, W., Lee, E.-W., Lee, D., Yang, M.-R., Ko, A., Yoon, C.-H., Lee, H.-W., Bae, Y.-S., Choi, C. Y. and Song, J. (2010). Hdm2 negatively regulates telomerase activity by functioning as an E3 ligase of hTERT. Oncogene 29, 4101-4112.
43. Palacios, I., Weis, K., Klebe, C., Mattaj, I. W. and Dingwall, C. (1996). RAN/TC4 mutants identify a common requirement for snRNP and protein import into the nucleus. J. Cell Biol. 133, 485-494.
44. Palm, W. and de Lange, T. (2008). How shelterin protects mammalian telomeres. Annu. Rev. Genet. 42, 301-334.
45. Peifer, M., Berg, S. and Reynolds, A. B. (1994). A repeating amino acid motif shared by proteins with diverse cellular roles. Cell 76, 789-791.
46. Pierce, M. M., Raman, C. S. and Nall, B. T. (1999). Isothermal titration calorimetry of protein-protein interactions. Methods 19, 213-221.
47. Poon, I. K. H. and Jans, D. A. (2005). Regulation of nuclear transport: central role in development and transformation? Traffic 6, 173-186.
48. Sfeir, A. and de Lange, T. (2012). Removal of shelterin reveals the telomere endprotection problem. Science 336, 593-597.
49. Smogorzewska, A. and de Lange, T. (2004). Regulation of telomerase by telomeric proteins. Annu. Rev. Biochem. 73, 177-208.
50. Stewart, M. (2007). Molecular mechanism of the nuclear protein import cycle. Nat. Rev. Mol. Cell. Biol. 8, 195-208.
51. Tarendeau, F., Boudet, J., Guilligay, D., Mas, P. J., Bougault, C. M., Boulo, S., Baudin, F., Ruigrok, R. W. H., Daigle, N., Ellenberg, J. et al. (2007). Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit. Nat. Struct. Mol. Biol. 14, 229-233.
52. Vagin, A. A., Steiner, R. A., Lebedev, A. A., Potterton, L., McNicholas, S., Long, F. and Murshudov, G. N. (2004). REFMAC 5 dictionary: organization of prior chemical knowledge and guidelines for its use. Acta Crystallogr. D. Biol. Crystallogr. 60, 2184-2195.
53. Venteicher, A. S., Meng, Z., Mason, P. J., Veenstra, T. D. and Artandi, S. E. (2008). Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly. Cell 132, 945-957.
54. Venteicher, A. S., Abreu, E. B., Meng, Z., McCann, K. E., Terns, R. M., Veenstra, T. D., Terns, M. P. and Artandi, S. E. (2009). A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science 323, 644-648.
55. Wang, J., Xie, L. Y., Allan, S., Beach, D. and Hannon, G. J. (1998). Myc activates telomerase. Genes Dev. 12, 1769-1774.
56. Xiao, C.-Y., Hübner, S. and Jans, D. A. (1997). SV40 large tumor antigen nuclear import is regulated by the double-stranded DNA-dependent protein kinase site (serine 120) flanking the nuclear localization sequence. J. Biol. Chem. 272, 22191-22198.