The interaction between Fe65 and Tip60 is regulated by S-nitrosylation on 440 cystein residue of Fe65
ABSTRACT
The S-Nitrosylation of protein thiol groups by NO is a widely recognized protein modification. The treat-ment of cells with NOBF4 induces the S-nitrosylation of FE65. In this study, we present evidence showing that FE65 modified by NO (Nitric Oxide) via S-nitrosylation induces functional changes in the protein that inhibits the HAT activity of Tip60. The results of mutational analysis of FE65 demonstrated further that the cysteine residue of FE65 (Cys440) is critical to the process of S-nitrosylation. The mutation of the cysteine residue which completely ablated the S-nitrosylation of FE65 also lost its inhibitory effects on Tip60 HAT activity. Thus, our findings show, for the first time, that the novel regulation mechanism of Tip60 activity may operate via FE65 binding, which is enhanced by S-nitrosylation on the FE65 Cys440 residue. This study describes the interaction between FE65 and Tip60, which is enhanced by a posttransla-tional modification of FE65 (through S-nitrosylation) by NO, promoting the association of the FE65-Tip60 protein complex and inhibiting both the HAT activity of Tip60 and cell death.
The S-Nitrosylation of protein thiol groups by NO is a widely recognized protein modification. The treat-ment of cells with NOBF4 induces the S-nitrosylation of FE65. In this study, we present evidence showing that FE65 modified by NO (Nitric Oxide) via S-nitrosylation induces functional changes in the protein that inhibits the HAT activity of Tip60. The results of mutational analysis of FE65 demonstrated further that the cysteine residue of FE65 (Cys440) is critical to the process of S-nitrosylation. The mutation of the cysteine residue which completely ablated the S-nitrosylation of FE65 also lost its inhibitory effects on Tip60 HAT activity. Thus, our findings show, for the first time, that the novel regulation mechanism of Tip60 activity may operate via FE65 binding, which is enhanced by S-nitrosylation on the FE65 Cys440 residue. This study describes the interaction between FE65 and Tip60, which is enhanced by a posttransla-tional modification of FE65 (through S-nitrosylation) by NO, promoting the association of the FE65-Tip60 protein complex and inhibiting both the HAT activity of Tip60 and cell death.
Cite this paper
nullLee, E. , Shin, S. , Hyun, S. , Chun, J. and Kang, S. (2011) The interaction between Fe65 and Tip60 is regulated by S-nitrosylation on 440 cystein residue of Fe65. Advances in Biological Chemistry, 1, 109-118. doi: 10.4236/abc.2011.13013.
nullLee, E. , Shin, S. , Hyun, S. , Chun, J. and Kang, S. (2011) The interaction between Fe65 and Tip60 is regulated by S-nitrosylation on 440 cystein residue of Fe65. Advances in Biological Chemistry, 1, 109-118. doi: 10.4236/abc.2011.13013.
References
[1] McLoughlin, D.M. and Miller, C.C. (2008) The FE65 proteins and Alzheimer’s disease. Journal of Neuroscience Research, 86, 744-754. doi:10.1002/jnr.21532 [2] Lee, E.J., Hyun, S.H., Chun, J. and Kang, S.S. (2007) Human NIMA-related kinase 6 is one of the Fe65 WW domain binding proteins. Biochemical and Biophysical Research Communications, 358, 783-788. doi:10.1016/j.bbrc.2007.04.203 [3] Lee, E.J., Hyun, S., Chun, J., Shin, S.H., Lee, K.E., Yeon, K.H., Park, T.Y. and Kang, S.S. (2008) The PPLA motif of glycogen synthase kinase 3beta is required for interac-tion with Fe65. Molecules and Cells, 26, 100-105. [4] Ermekova, K.S., Zambrano, N., Linn, H., Minopoli, G., Gertler, F., Russo, T. and Sudol, M. (1997) The WW do-main of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled. Journal of Biological Chemistry, 272, 32869- 32877. doi:10.1074/jbc.272.52.32869 [5] Sudol, M., Sliwa, K. and Russo, T. (2001) Functions of WW domains in the nucleus. FEBS Letters, 490, 190- 195. doi:10.1016/S0014-5793(01)02122-6 [6] Gordge, M.P. and Xiao, F. (2010) S-nitrosothiols as se-lective antithrombotic agents-possible mechanisms. British Journal of Pharmacology, 159, 1572-1580. doi:10.1111/j.1476-5381.2010.00670.x [7] Lima, B., Forrester, M.T., Hess, D.T., and Stamler, J.S. (2010) S-nitrosylation in cardiovascular signaling. Cir-culation Research, 106, 633-646. doi:10.1161/CIRCRESAHA.109.207381 [8] Sun, J. and Murphy, E. (2010) Protein S-nitrosylation and cardioprotection. Circulation Research, 106, 285- 296. doi:10.1161/CIRCRESAHA.109.209452 [9] Arnelle, D.R. and Stamler, J.S. (1995) NO+, NO, and NO-donation by S-nitrosothiols: implications for regula-tion of physiological functions by S-nitrosylation and acceleration of disulfide formation. Archives of Bioche-mistry and Biophysics, 318, 279-285. doi:10.1006/abbi.1995.1231 [10] Stamler, J.S., Simon, D.I., Jaraki, O., Osborne, J.A., Francis, S., Mullins, M., Singel, D. and Loscalzo, J. (1992) S-nitrosylation of tissue-type plasminogen acti-vator confers vasodilatory and antiplatelet properties on the enzyme. Proceedings of the National Academy of Sciences of the USA, 89, 8087-8091. doi:10.1073/pnas.89.17.8087 [11] Fukuda, H., Fukuda, A., Zhu, C., Korhonen, L., Swan-palmer, J., Hertzman, S., Leist, M., Lannering, B., Lind-holm, D., Bjork-Eriksson, T., Marky, I., and Blomgren, K. (2004) Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition. Cell Death and Differentiation, 11, 1166-1178. doi:10.1038/sj.cdd.4401472 [12] Lipton, S.A., Choi, Y.B., Pan, Z.H., Lei, S.Z., Chen, H.S., Sucher, N.J., Loscalzo, J., Singel, D.J. and Stamler, J.S. (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature, 364, 626-632. doi:10.1038/364626a0 [13] Lander, H.M., Ogiste, J.S., Pearce, S.F., Levi, R. and Novogrodsky, A. (1995) Nitric oxide-stimulated guanine nucleotide exchange on p21ras. Journal of Biological Chemistry, 270, 7017-7020. doi:10.1074/jbc.270.13.7017 [14] Yoshida, T., Inoue, R., Morii, T., Takahashi, N., Yama-moto, S., Hara, Y., Tominaga, M., Shimizu, S., Sato, Y. and Mori, Y. (2006) Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nature Chemical Biology, 2, 596-607. doi:10.1038/nchembio821 [15] Chander, M., and Demple, B. (2004) Functional analysis of SoxR residues affecting transduction of oxidative stress signals into gene expression. Journal of Biological Chemistry, 279, 41603-41610. doi:10.1074/jbc.M405512200 [16] Gu, Z., Nakamura, T. and Lipton, S.A. (2010) Redox reactions induced by nitrosative stress mediate protein misfolding and mitochondrial dysfunction in neurodege-nerative diseases. Molecular Neurobiology, 41, 55-72. doi:10.1007/s12035-010-8113-9 [17] Russo, T., Faraonio, R., Minopoli, G., De Candia, P., De Renzis, S. and Zambrano, N. (1998) Fe65 and the protein network centered around the cytosolic domain of the Alzheimer’s beta-amyloid precursor protein, FEBS Let-ters,434, 1-7. doi:10.1016/S0014-5793(98)00941-7 [18] Chen, H.I. and Sudol, M. (1995) The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules. Proceedings of the National Academy of Sciences of the USA, 92, 7819- 7823. doi:10.1073/pnas.92.17.7819 [19] Fiore, F., Zambrano, N., Minopoli, G., Donini, V., Duilio, A. and Russo, T. (1995) The regions of the Fe65 protein homologous to the phosphotyrosine interaction/phos- phortyrosine binding domain of Shc bind the intracellular domain of the Alzheimer’s amyloid precursor protein, Journal of Biological Chemistry, 270, 30853-30856. [20] Zambrano, N., Minopoli, G., de Candia, P. and Russo, T. (1998) The Fe65 adaptor protein interacts through its PID1 domain with the transcription factor CP2/LSF/ LBP1. Journal of Biological Chemistry, 273, 20128- 20133. doi:10.1074/jbc.273.32.20128
[1] McLoughlin, D.M. and Miller, C.C. (2008) The FE65 proteins and Alzheimer’s disease. Journal of Neuroscience Research, 86, 744-754. doi:10.1002/jnr.21532 [2] Lee, E.J., Hyun, S.H., Chun, J. and Kang, S.S. (2007) Human NIMA-related kinase 6 is one of the Fe65 WW domain binding proteins. Biochemical and Biophysical Research Communications, 358, 783-788. doi:10.1016/j.bbrc.2007.04.203 [3] Lee, E.J., Hyun, S., Chun, J., Shin, S.H., Lee, K.E., Yeon, K.H., Park, T.Y. and Kang, S.S. (2008) The PPLA motif of glycogen synthase kinase 3beta is required for interac-tion with Fe65. Molecules and Cells, 26, 100-105. [4] Ermekova, K.S., Zambrano, N., Linn, H., Minopoli, G., Gertler, F., Russo, T. and Sudol, M. (1997) The WW do-main of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled. Journal of Biological Chemistry, 272, 32869- 32877. doi:10.1074/jbc.272.52.32869 [5] Sudol, M., Sliwa, K. and Russo, T. (2001) Functions of WW domains in the nucleus. FEBS Letters, 490, 190- 195. doi:10.1016/S0014-5793(01)02122-6 [6] Gordge, M.P. and Xiao, F. (2010) S-nitrosothiols as se-lective antithrombotic agents-possible mechanisms. British Journal of Pharmacology, 159, 1572-1580. doi:10.1111/j.1476-5381.2010.00670.x [7] Lima, B., Forrester, M.T., Hess, D.T., and Stamler, J.S. (2010) S-nitrosylation in cardiovascular signaling. Cir-culation Research, 106, 633-646. doi:10.1161/CIRCRESAHA.109.207381 [8] Sun, J. and Murphy, E. (2010) Protein S-nitrosylation and cardioprotection. Circulation Research, 106, 285- 296. doi:10.1161/CIRCRESAHA.109.209452 [9] Arnelle, D.R. and Stamler, J.S. (1995) NO+, NO, and NO-donation by S-nitrosothiols: implications for regula-tion of physiological functions by S-nitrosylation and acceleration of disulfide formation. Archives of Bioche-mistry and Biophysics, 318, 279-285. doi:10.1006/abbi.1995.1231 [10] Stamler, J.S., Simon, D.I., Jaraki, O., Osborne, J.A., Francis, S., Mullins, M., Singel, D. and Loscalzo, J. (1992) S-nitrosylation of tissue-type plasminogen acti-vator confers vasodilatory and antiplatelet properties on the enzyme. Proceedings of the National Academy of Sciences of the USA, 89, 8087-8091. doi:10.1073/pnas.89.17.8087 [11] Fukuda, H., Fukuda, A., Zhu, C., Korhonen, L., Swan-palmer, J., Hertzman, S., Leist, M., Lannering, B., Lind-holm, D., Bjork-Eriksson, T., Marky, I., and Blomgren, K. (2004) Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition. Cell Death and Differentiation, 11, 1166-1178. doi:10.1038/sj.cdd.4401472 [12] Lipton, S.A., Choi, Y.B., Pan, Z.H., Lei, S.Z., Chen, H.S., Sucher, N.J., Loscalzo, J., Singel, D.J. and Stamler, J.S. (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature, 364, 626-632. doi:10.1038/364626a0 [13] Lander, H.M., Ogiste, J.S., Pearce, S.F., Levi, R. and Novogrodsky, A. (1995) Nitric oxide-stimulated guanine nucleotide exchange on p21ras. Journal of Biological Chemistry, 270, 7017-7020. doi:10.1074/jbc.270.13.7017 [14] Yoshida, T., Inoue, R., Morii, T., Takahashi, N., Yama-moto, S., Hara, Y., Tominaga, M., Shimizu, S., Sato, Y. and Mori, Y. (2006) Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nature Chemical Biology, 2, 596-607. doi:10.1038/nchembio821 [15] Chander, M., and Demple, B. (2004) Functional analysis of SoxR residues affecting transduction of oxidative stress signals into gene expression. Journal of Biological Chemistry, 279, 41603-41610. doi:10.1074/jbc.M405512200 [16] Gu, Z., Nakamura, T. and Lipton, S.A. (2010) Redox reactions induced by nitrosative stress mediate protein misfolding and mitochondrial dysfunction in neurodege-nerative diseases. Molecular Neurobiology, 41, 55-72. doi:10.1007/s12035-010-8113-9 [17] Russo, T., Faraonio, R., Minopoli, G., De Candia, P., De Renzis, S. and Zambrano, N. (1998) Fe65 and the protein network centered around the cytosolic domain of the Alzheimer’s beta-amyloid precursor protein, FEBS Let-ters,434, 1-7. doi:10.1016/S0014-5793(98)00941-7 [18] Chen, H.I. and Sudol, M. (1995) The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules. Proceedings of the National Academy of Sciences of the USA, 92, 7819- 7823. doi:10.1073/pnas.92.17.7819 [19] Fiore, F., Zambrano, N., Minopoli, G., Donini, V., Duilio, A. and Russo, T. (1995) The regions of the Fe65 protein homologous to the phosphotyrosine interaction/phos- phortyrosine binding domain of Shc bind the intracellular domain of the Alzheimer’s amyloid precursor protein, Journal of Biological Chemistry, 270, 30853-30856. [20] Zambrano, N., Minopoli, G., de Candia, P. and Russo, T. (1998) The Fe65 adaptor protein interacts through its PID1 domain with the transcription factor CP2/LSF/ LBP1. Journal of Biological Chemistry, 273, 20128- 20133. doi:10.1074/jbc.273.32.20128