Cdk5 activity in the brain - multiple paths of regulation

Journal of Cell Science

Volumn 127, Issue 11, 2014, Pages 2407-2419

  Shah, Kavita ^a   Lahiri, Debomoy K ^b  

^a Department of Chemistry ^*  (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Alzheimer's disease; Axonal growth; Cdk; Cdk5; Cyclins; Excitotoxicity; Learning and memory; Neurodegeneration; Neuronal migration; P25; P35; Pain signalling; Synaptic plasticity; Synaptogenesis; Amyloid

Indexed keywords

CYCLIN D; CYCLIN DEPENDENT KINASE 5; CYCLIN E; CYCLIN I; GLUTATHIONE TRANSFERASE P1; P29 PROTEIN; PROTEIN; PROTEIN P10; PROTEIN P25; PROTEIN P35; PROTEIN P39; UNCLASSIFIED DRUG;

ARTICLE; BRAIN; DRUG DEPENDENCE; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; HUMAN; NERVE CELL PLASTICITY; NEUROLOGIC DISEASE; NITROSYLATION; NONHUMAN; PAIN; PRIORITY JOURNAL; REGULATORY MECHANISM; TRANSCRIPTION REGULATION;

EID: 84901774150     PISSN: 00219533     EISSN: 14779137     Source Type: Journal    
DOI: 10.1242/jcs.130344     Document Type: Article

References (129)

1. Absalon, S., Kochanek, D. M., Raghavan, V. and Krichevsky, A. M. (2013). MiR-26b, upregulated in Alzheimer's disease, activates cell cycle entry, tauphosphorylation, and apoptosis in postmitotic neurons. J. Neurosci. 33, 14645-14659.
2. Anglade, P., Vyas, S., Javoy-Agid, F., Herrero, M. T., Michel, P. P., Marquez, J., Mouatt-Prigent, A., Ruberg, M., Hirsch, E. C. and Agid, Y. (1997). Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease. Histol. Histopathol. 12, 25-31.
3. Asada, A., Yamamoto, N., Gohda, M., Saito, T., Hayashi, N. and Hisanaga, S. (2008). Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cyclin-dependent kinase 5 complexes. J. Neurochem. 106, 1325-1336.
4. Asada, A., Saito, T. and Hisanaga, S. (2012). Phosphorylation of p35 and p39 by Cdk5 determines the subcellular location of the holokinase in a phosphorylationsite-specific manner. J. Cell Sci. 125, 3421-3429.
5. Bates, S., Bonetta, L., MacAllan, D., Parry, D., Holder, A., Dickson, C. and Peters, G. (1994). CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1. Oncogene 9, 71-79.
6. Berhane, K., Widersten, M., Engström, A., Kozarich, J. W. and Mannervik, B. (1994). Detoxication of base propenals and other alpha, beta-unsaturated aldehyde products of radical reactions and lipid peroxidation by human glutathione transferases. Proc. Natl. Acad. Sci. USA 91, 1480-1484.
7. Bibb, J. A., Chen, J., Taylor, J. R., Svenningsson, P., Nishi, A., Snyder, G. L., Yan, Z., Sagawa, Z. K., Ouimet, C. C., Nairn, A. C. et al. (2001). Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 410, 376-380.
8. Bogush, A., Pedrini, S., Pelta-Heller, J., Chan, T., Yang, Q., Mao, Z., Sluzas, E., Gieringer, T. and Ehrlich, M. E. (2007). AKT and CDK5/p35 mediate brainderived neurotrophic factor induction of DARPP-32 in medium size spiny neurons in vitro. J. Biol. Chem. 282, 7352-7359.
9. Brinkkoetter, P. T., Olivier, P., Wu, J. S., Henderson, S., Krofft, R. D., Pippin, J. W., Hockenbery, D., Roberts, J. M. and Shankland, S. J. (2009). Cyclin I activates Cdk5 and regulates expression of Bcl-2 and Bcl-XL in postmitotic mouse cells. J. Clin. Invest. 119, 3089-3101.
10. Brinkkoetter, P. T., Pippin, J. W. and Shankland, S. J. (2010). Cyclin I-Cdk5 governs survival in post-mitotic cells. Cell Cycle 9, 1729-1731.
11. Cancino, G. I., Perez de Arce, K., Castro, P. U., Toledo, E. M., von Bernhardi, R. and Alvarez, A. R. (2011). c-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice. Neurobiol. Aging 32, 1249-1261.
12. Chang, Y., Ostling, P., Akerfelt, M., Trouillet, D., Rallu, M., Gitton, Y., El Fatimy, R., Fardeau, V., Le Crom, S., Morange, M. et al. (2006). Role of heat-shock factor 2 in cerebral cortex formation and as a regulator of p35 expression. Genes Dev. 20, 836-847.
13. Chang, K. H., de Pablo, Y., Lee, H. P., Lee, H. G., Smith, M. A. and Shah, K. (2010). Cdk5 is a major regulator of p38 cascade: relevance to neurotoxicity in Alzheimer's disease. J. Neurochem. 113, 1221-1229.
14. Chang, K. H., Multani, P. S., Sun, K. H., Vincent, F., de Pablo, Y., Ghosh, S., Gupta, R., Lee, H. P., Lee, H. G., Smith, M. A. et al. (2011). Nuclear envelope dispersion triggered by deregulated Cdk5 precedes neuronal death. Mol. Biol. Cell 22, 1452-1462.
15. Chang, K. H., Vincent, F. and Shah, K. (2012). Deregulated Cdk5 triggers aberrant activation of cell cycle kinases and phosphatases inducing neuronal death. J. Cell Sci. 125, 5124-5137.
16. Chen, J., Zhang, Y., Kelz, M. B., Steffen, C., Ang, E. S., Zeng, L. and Nestler, E. J. (2000). Induction of cyclin-dependent kinase 5 in the hippocampus by chronic electroconvulsive seizures: role of [Delta]FosB. J. Neurosci. 20, 8965-8971.
17. Chen, F., Wang, Q., Wang, X. and Studzinski, G. P. (2004). Up-regulation of Egr1 by 1,25-dihydroxyvitamin D3 contributes to increased expression of p35 activator of cyclin-dependent kinase 5 and consequent onset of the terminal phase of HL60 cell differentiation. Cancer Res. 64, 5425-5433.
18. Cheng, Q., Sasaki, Y., Shoji, M., Sugiyama, Y., Tanaka, H., Nakayama, T., Mizuki, N., Nakamura, F., Takei, K. and Goshima, Y. (2003). Cdk5/p35 and Rho-kinase mediate ephrin-A5-induced signaling in retinal ganglion cells. Mol. Cell. Neurosci. 24, 632-645.
19. Cheung, Z. H. and Ip, N. Y. (2012). Cdk5: a multifaceted kinase in neurodegenerative diseases. Trends Cell Biol. 22, 169-175.
20. Cruz, J. C., Tseng, H. C., Goldman, J. A., Shih, H. and Tsai, L. H. (2003). Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40, 471-483.
21. De Falco, M., Fedele, V., De Luca, L., Penta, R., Cottone, G., Cavallotti, I., Laforgia, V. and De Luca, A. (2004). Evaluation of cyclin D1 expression and its subcellular distribution in mouse tissues. J. Anat. 205, 405-412.
22. Desbarats, J., Birge, R. B., Mimouni-Rongy, M., Weinstein, D. E., Palerme, J. S. and Newell, M. K. (2003). Fas engagement induces neurite growth through ERK activation and p35 upregulation. Nat. Cell Biol. 5, 118-125.
23. Dhavan, R. and Tsai, L. H. (2001). A decade of CDK5. Nat. Rev. Mol. Cell Biol. 2, 749-759.
24. Elledge, S. J. and Spottswood, M. R. (1991). A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1. EMBO J. 10, 2653-2659.
25. Fattaey, A. and Booher, R. N. (1997). Myt1: a Wee1-type kinase that phosphorylates Cdc2 on residue Thr14. Prog. Cell Cycle Res. 3, 233-240.
26. Fischer, A., Sananbenesi, F., Schrick, C., Spiess, J. and Radulovic, J. (2002). Cyclin-dependent kinase 5 is required for associative learning. J. Neurosci. 22, 3700-3707.
27. Fu, X., Choi, Y. K., Qu, D., Yu, Y., Cheung, N. S. and Qi, R. Z. (2006). Identification of nuclear import mechanisms for the neuronal Cdk5 activator. J. Biol. Chem. 281, 39014-39021.
28. Glicksman, M. A., Cuny, G. D., Liu, M., Dobson, B., Auerbach, K., Stein, R. L. and Kosik, K. S. (2007). New approaches to the discovery of cdk5 inhibitors. Curr. Alzheimer Res. 4, 547-549.
29. Guan, J. S., Su, S. C., Gao, J., Joseph, N., Xie, Z., Zhou, Y., Durak, O., Zhang, L., Zhu, J. J., Clauser, K. R. et al. (2011). Cdk5 is required for memory function and hippocampal plasticity via the cAMP signaling pathway. PLoS ONE 6, e25735.
30. Guidato, S., McLoughlin, D. M., Grierson, A. J. and Miller, C. C. (1998). Cyclin D2 interacts with cdk-5 and modulates cellular cdk-5/p35 activity. J. Neurochem. 70, 335-340.
31. Harada, T., Morooka, T., Ogawa, S. and Nishida, E. (2001). ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1. Nat. Cell Biol. 3, 453-459.
32. Hawasli, A. H., Benavides, D. R., Nguyen, C., Kansy, J. W., Hayashi, K., Chambon, P., Greengard, P., Powell, C. M., Cooper, D. C. and Bibb, J. A. (2007). Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation. Nat. Neurosci. 10, 880-886.
33. He, L., Hou, Z. and Qi, R. Z. (2008). Calmodulin binding and Cdk5 phosphorylation of p35 regulate its effect on microtubules. J. Biol. Chem. 283, 13252-13260.
34. Heisler, F. F., Loebrich, S., Pechmann, Y., Maier, N., Zivkovic, A. R., Tokito, M., Hausrat, T. J., Schweizer, M., Bähring, R., Holzbaur, E. L. et al. (2011). Muskelin regulates actin filament- and microtubule-based GABA(A) receptor transport in neurons. Neuron 70, 66-81.
35. Hellmich, M. R., Pant, H. C., Wada, E. and Battey, J. F. (1992). Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression. Proc. Natl. Acad. Sci. USA 89, 10867-10871.
36. Hisanaga, S. and Endo, R. (2010). Regulation and role of cyclin-dependent kinase activity in neuronal survival and death. J. Neurochem. 115, 1309-1321.
37. Ishiguro, K., Takamatsu, M., Tomizawa, K., Omori, A., Takahashi, M., Arioka, M., Uchida, T. and Imahori, K. (1992). Tau protein kinase I converts normal tau protein into A68-like component of paired helical filaments. J. Biol. Chem. 267, 10897-10901.
38. Jeong, Y. G., Rosales, J. L., Marzban, H., Sillitoe, R. V., Park, D. G., Hawkes, R. and Lee, K. Y. (2003). The cyclin-dependent kinase 5 activator, p39, is expressed in stripes in the mouse cerebellum. Neuroscience 118, 323-334.
39. Kamei, H., Saito, T., Ozawa, M., Fujita, Y., Asada, A., Bibb, J. A., Saido, T. C., Sorimachi, H. and Hisanaga, S. (2007). Suppression of calpain-dependent cleavage of the CDK5 activator p35 to p25 by site-specific phosphorylation. J. Biol. Chem. 282, 1687-1694.
40. Kelz, M. B. and Nestler, E. J. (2000). deltaFosB: a molecular switch underlying long-term neural plasticity. Curr. Opin. Neurol. 13, 715-720.
41. Ko, J., Humbert, S., Bronson, R. T., Takahashi, S., Kulkarni, A. B., Li, E. and Tsai, L. H. (2001). p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. J. Neurosci. 21, 6758-6771.
42. Koff, A., Cross, F., Fisher, A., Schumacher, J., Leguellec, K., Philippe, M. and Roberts, J. M. (1991). Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell 66, 1217-1228.
43. Lahiri, D. K. (2011). An integrated approach to genome studies. Science 331, 147.
44. Lahiri, D. K., Farlow, M. R., Sambamurti, K., Greig, N. H., Giacobini, E. and Schneider, L. S. (2003). A critical analysis of new molecular targets and strategies for drug developments in Alzheimer's disease. Curr. Drug Targets 4, 97-112.
45. Lahiri, D. K., Maloney, B., Long, J. M. and Greig, N. H. (2014). Lessons from a BACE1 inhibitor trial: Off-site but not off base. Alzheimers Dement. [Epub Ahead of Print]
46. Ledee, D. R., Gao, C. Y., Seth, R., Fariss, R. N., Tripathi, B. K. and Zelenka, P. S. (2005). A specific interaction between muskelin and the cyclin-dependent kinase 5 activator p39 promotes peripheral localization of muskelin. J. Biol. Chem. 280, 21376-21383.
47. Lee, J. H. and Kim, K. T. (2004). Induction of cyclin-dependent kinase 5 and its activator p35 through the extracellular-signal-regulated kinase and protein kinase A pathways during retinoic-acid mediated neuronal differentiation in human neuroblastoma SK-N-BE(2)C cells. J. Neurochem. 91, 634-647.
48. Lee, M. G. and Nurse, P. (1987). Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature 327, 31-35.
49. Lee, K. Y., Clark, A. W., Rosales, J. L., Chapman, K., Fung, T. and Johnston, R. N. (1999). Elevated neuronal Cdc2-like kinase activity in the Alzheimer disease brain. Neurosci. Res. 34, 21-29.
50. Lee, M. S., Kwon, Y. T., Li, M., Peng, J., Friedlander, R. M. and Tsai, L. H. (2000). Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature 405, 360-364.
51. Lew, J., Beaudette, K., Litwin, C. M. and Wang, J. H. (1992). Purification and characterization of a novel proline-directed protein kinase from bovine brain. J. Biol. Chem. 267, 13383-13390.
52. Lew, J., Huang, Q. Q., Qi, Z., Winkfein, R. J., Aebersold, R., Hunt, T. and Wang, J. H. (1994). A brain-specific activator of cyclin-dependent kinase 5. Nature 371, 423-426.
53. Lim, J. Y., Park, S. I., Oh, J. H., Kim, S. M., Jeong, C. H., Jun, J. A., Lee, K. S., Oh, W., Lee, J. K. and Jeun, S. S. (2008). Brain-derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through MAPK/ERK and PI3K/Akt-dependent signaling pathways. J. Neurosci. Res. 86, 2168-2178.
54. Lin, H., Lin, T. Y. and Juang, J. L. (2007). Abl deregulates Cdk5 kinase activity and subcellular localization in Drosophila neurodegeneration. Cell Death Differ. 14, 607-615.
55. Long, J. M. and Lahiri, D. K. (2011a). MicroRNA-101 downregulates Alzheimer's amyloid-b precursor protein levels in human cell cultures and is differentially expressed. Biochem. Biophys. Res. Commun. 404, 889-895.
56. Long, J. M. and Lahiri, D. K. (2011b). Current drug targets for modulating Alzheimer's amyloid precursor protein: role of specific micro-RNA species. Curr. Med. Chem. 18, 3314-3321.
57. Long, J. M. and Lahiri, D. K. (2012). Advances in microRNA experimental approaches to study physiological regulation of gene products implicated in CNS disorders. Exp. Neurol. 235, 402-418.
58. Long, J. M., Ray, B. and Lahiri, D. K. (2012). MicroRNA-153 physiologically inhibits expression of amyloid-b precursor protein in cultured human fetal brain cells and is dysregulated in a subset of Alzheimer disease patients. J. Biol. Chem. 287, 31298-31310.
59. Long, J. M., Ray, B. and Lahiri, D. K. (2014). MicroRNA-339-5p downregulates protein expression of the b-site amyloid precursor protein cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer's disease subjects. J. Biol. Chem. 289, 5184-5198.
60. Lopes, J. P., Oliveira, C. R. and Agostinho, P. (2010). Neurodegeneration in an Abeta-induced model of Alzheimer's disease: the role of Cdk5. Aging Cell 9, 64-77.
61. Lovell, M. A., Xie, C. and Markesbery, W. R. (1998). Decreased glutathione transferase activity in brain and ventricular fluid in Alzheimer's disease. Neurology 51, 1562-1566.
62. Malumbres, M., Harlow, E., Hunt, T., Hunter, T., Lahti, J. M., Manning, G., Morgan, D. O., Tsai, L. H. and Wolgemuth, D. J. (2009). Cyclin-dependent kinases: a family portrait. Nat. Cell Biol. 11, 1275-1276.
63. McEvilly, R. J., de Diaz, M. O., Schonemann, M. D., Hooshmand, F. and Rosenfeld, M. G. (2002). Transcriptional regulation of cortical neuron migration by POU domain factors. Science 295, 1528-1532.
64. Menn, B., Bach, S., Blevins, T. L., Campbell, M., Meijer, L. and Timsit, S. (2010). Delayed treatment with systemic (S)-roscovitine provides neuroprotection and inhibits in vivo CDK5 activity increase in animal stroke models. PLoS ONE 5, e12117.
65. Meyerson, M., Enders, G. H., Wu, C. L., Su, L. K., Gorka, C., Nelson, C., Harlow, E. and Tsai, L. H. (1992). A family of human cdc2-related protein kinases. EMBO J. 11, 2909-2917.
66. Minegishi, S., Asada, A., Miyauchi, S., Fuchigami, T., Saito, T. and Hisanaga, S. (2010). Membrane association facilitates degradation and cleavage of the cyclin-dependent kinase 5 activators p35 and p39. Biochemistry 49, 5482-5493.
67. Mitsios, N., Pennucci, R., Krupinski, J., Sanfeliu, C., Gaffney, J., Kumar, P., Kumar, S., Juan-Babot, O. and Slevin, M. (2007). Expression of cyclindependent kinase 5 mRNA and protein in the human brain following acute ischemic stroke. Brain Pathol. 17, 11-23.
68. Modi, P. K., Komaravelli, N., Singh, N. and Sharma, P. (2012). Interplay between MEK-ERK signaling, cyclin D1, and cyclin-dependent kinase 5 regulates cell cycle reentry and apoptosis of neurons. Mol. Biol. Cell 23, 3722-3730.
69. Monaco, E. A., III (2004). Recent evidence regarding a role for Cdk5 dysregulation in Alzheimer's disease. Curr. Alzheimer Res. 1, 33-38.
70. Moncini, S., Salvi, A., Zuccotti, P., Viero, G., Quattrone, A., Barlati, S., De Petro, G., Venturin, M. and Riva, P. (2011). The role of miR-103 and miR-107 in regulation of CDK5R1 expression and in cellular migration. PLoS ONE 6, e20038.
71. Nagano, T., Hashimoto, T., Nakashima, A., Hisanaga, S., Kikkawa, U. and Kamada, S. (2013). Cyclin I is involved in the regulation of cell cycle progression. Cell Cycle 12, 2617-2624.
72. Nakamura, T., Sanokawa, R., Sasaki, Y. F., Ayusawa, D., Oishi, M. and Mori, N. (1995). Cyclin I: a new cyclin encoded by a gene isolated from human brain. Exp. Cell Res. 221, 534-542.
73. Ninomiya-Tsuji, J., Nomoto, S., Yasuda, H., Reed, S. I. and Matsumoto, K. (1991). Cloning of a human cDNA encoding a CDC2-related kinase by complementation of a budding yeast cdc28 mutation. Proc. Natl. Acad. Sci. USA 88, 9006-9010.
74. Nishi, A., Bibb, J. A., Snyder, G. L., Higashi, H., Nairn, A. C. and Greengard, P. (2000). Amplification of dopaminergic signaling by a positive feedback loop. Proc. Natl. Acad. Sci. USA 97, 12840-12845.
75. Nixon, R. A. (2003). The calpains in aging and aging-related diseases. Ageing Res. Rev. 2, 407-418.
76. Odajima, J., Wills, Z. P., Ndassa, Y. M., Terunuma, M., Kretschmannova, K., Deeb, T. Z., Geng, Y., Gawrzak, S., Quadros, I. M., Newman, J. et al. (2011). Cyclin E constrains Cdk5 activity to regulate synaptic plasticity and memory formation. Dev. Cell 21, 655-668.
77. Ohshima, T., Ward, J. M., Huh, C. G., Longenecker, G., Veeranna, Pant, H. C, Brady, R. O, Martin, L. J. and Kulkarni, A. B. (1996). Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc. Natl. Acad. Sci. USA 93, 11173-11178.
78. Ohshima, T., Ogura, H., Tomizawa, K., Hayashi, K., Suzuki, H., Saito, T., Kamei, H., Nishi, A., Bibb, J. A.., Hisanaga, S., Matsui, H. and Mikoshiba, K. (2005). Impairment of hippocampal long-term depression and defective spatial learning and memory in p35 mice. J. Neurochem. 94, 917-925.
79. Paglini, G., Pigino, G., Kunda, P., Morfini, G., Maccioni, R., Quiroga, S., Ferreira, A. and Cáceres, A. (1998). Evidence for the participation of the neuron-specific CDK5 activator P35 during laminin-enhanced axonal growth. J. Neurosci. 18, 9858-9869.
80. Paoletti, P., Vila, I., Rifé, M., Lizcano, J. M., Alberch, J. and Ginés, S. (2008). Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25/cyclin-dependent kinase 5. J. Neurosci. 28, 10090-10101.
81. Pareek, T. K., Keller, J., Kesavapany, S., Pant, H. C., Iadarola, M. J., Brady, R. O. and Kulkarni, A. B. (2006). Cyclin-dependent kinase 5 activity regulates pain signaling. Proc. Natl. Acad. Sci. USA 103, 791-796.
82. Pareek, T. K., Keller, J., Kesavapany, S., Agarwal, N., Kuner, R., Pant, H. C., Iadarola, M. J., Brady, R. O. and Kulkarni, A. B. (2007). Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc. Natl. Acad. Sci. USA 104, 660-665.
83. Patrick, G. N., Zukerberg, L., Nikolic, M., de la Monte, S., Dikkes, P. and Tsai, L. H. (1999). Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402, 615-622.
84. Patzke, H. and Tsai, L. H. (2002). Calpain-mediated cleavage of the cyclindependent kinase-5 activator p39 to p29. J. Biol. Chem. 277, 8054-8060.
85. Perez, F. P., Bose, D., Maloney, B., Nho, K., Shah, K. and Lahiri, D. K. (2014). Late-Onset Alzheimer's Disease, Heating up and Foxed by Several Proteins: Pathomolecular Effects of the Aging Process. J. Alzheimers Dis. 40, 1-17.
86. Peterson, D. W., Ando, D. M., Taketa, D. A., Zhou, H., Dahlquist, F. W. and Lew, J. (2010). No difference in kinetics of tau or histone phosphorylation by CDK5/p25 versus CDK5/p35 in vitro. Proc. Natl. Acad. Sci. USA 107, 2884-2889.
87. Poon, R. Y., Lew, J. and Hunter, T. (1997). Identification of functional domains in the neuronal Cdk5 activator protein. J. Biol. Chem. 272, 5703-5708.
88. Qu, J., Nakamura, T., Cao, G., Holland, E. A., McKercher, S. R. and Lipton, S. A. (2011). S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by beta-amyloid peptide. Proc. Natl. Acad. Sci. USA 108, 14330-14335.
89. Qu, J., Nakamura, T., Holland, E. A., McKercher, S. R. and Lipton, S. A. (2012). S-nitrosylation of Cdk5: potential implications in amyloid-b-related neurotoxicity in Alzheimer disease. Prion 6, 364-370.
90. Rosenmann, H. (2013). Immunotherapy for targeting tau pathology in Alzheimer's disease and tauopathies. Curr. Alzheimer Res. 10, 217-228.
91. Sahlgren, C. M., Pallari, H. M., He, T., Chou, Y. H., Goldman, R. D. and Eriksson, J. E. (2006). A nestin scaffold links Cdk5/p35 signaling to oxidantinduced cell death. EMBO J. 25, 4808-4819.
92. Saito, K., Elce, J. S., Hamos, J. E. and Nixon, R. A. (1993). Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration. Proc. Natl. Acad. Sci. USA 90, 2628-2632.
93. Sasaki, Y., Cheng, C., Uchida, Y., Nakajima, O., Ohshima, T., Yagi, T., Taniguchi, M., Nakayama, T., Kishida, R., Kudo, Y. et al. (2002). Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex. Neuron 35, 907-920.
94. Sato, S., Xu, J., Okuyama, S., Martinez, L. B., Walsh, S. M., Jacobsen, M. T., Swan, R. J., Schlautman, J. D., Ciborowski, P. and Ikezu, T. (2008). Spatial learning impairment, enhanced CDK5/p35 activity, and downregulation of NMDA receptor expression in transgenic mice expressing tau-tubulin kinase 1. J. Neurosci. 28, 14511-14521.
95. Sato, K., Minegishi, S., Takano, J., Plattner, F., Saito, T., Asada, A., Kawahara, H., Iwata, N., Saido, T. C. and Hisanaga, S. (2011). Calpastatin, an endogenous calpain-inhibitor protein, regulates the cleavage of the Cdk5 activator p35 to p25. J. Neurochem. 117, 504-515.
96. Sharma, P., Veeranna, Sharma, M., Amin, N. D., Sihag, R. K., Grant, P., Ahn, N., Kulkarni, A. B. and Pant, H. C. (2002). Phosphorylation of MEK1 by cdk5/ p35 down-regulates the mitogen-activated protein kinase pathway. J. Biol. Chem. 277, 528-534.
97. Shea, T. B., Yabe, J. T., Ortiz, D., Pimenta, A., Loomis, P., Goldman, R. D., Amin, N. and Pant, H. C. (2004). Cdk5 regulates axonal transport and phosphorylation of neurofilaments in cultured neurons. J. Cell Sci. 117, 933-941.
98. Smith, P. D., Crocker, S. J., Jackson-Lewis, V., Jordan-Sciutto, K. L., Hayley, S., Mount, M. P., O'Hare, M. J., Callaghan, S., Slack, R. S., Przedborski, S. et al. (2003). Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 100, 13650-13655.
99. Song, J. H., Wang, C. X., Song, D. K., Wang, P., Shuaib, A. and Hao, C. (2005). Interferon gamma induces neurite outgrowth by up-regulation of p35 neuron-specific cyclin-dependent kinase 5 activator via activation of ERK1/2 pathway. J. Biol. Chem. 280, 12896-12901.
100. Sun, K. H., de Pablo, Y., Vincent, F., Johnson, E. O., Chavers, A. K. and Shah, K. (2008a). Novel genetic tools reveal Cdk5's major role in Golgi fragmentation in Alzheimer's disease. Mol. Biol. Cell 19, 3052-3069.
101. Sun, K. H., de Pablo, Y., Vincent, F. and Shah, K. (2008b). Deregulated Cdk5 promotes oxidative stress and mitochondrial dysfunction. J. Neurochem. 107, 265-278.
102. Sun, K. H., Lee, H. G., Smith, M. A. and Shah, K. (2009). Direct and indirect roles of cyclin-dependent kinase 5 as an upstream regulator in the c-Jun NH2-terminal kinase cascade: relevance to neurotoxic insults in Alzheimer's Disease. Mol. Biol. Cell 20, 4611-4619.
103. Sun, K. H., Chang, K. H., Clawson, S., Ghosh, S., Mirzaei, H., Regnier, F. and Shah, K. (2011). Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activity. J. Neurochem. 118, 902-914.
104. Sundaram, J. R., Poore, C. P., Sulaimee, N. H., Pareek, T., Asad, A. B., Rajkumar, R., Cheong, W. F., Wenk, M. R., Dawe, G. S., Chuang, K. H. et al. (2013). Specific inhibition of p25/Cdk5 activity by the Cdk5 inhibitory peptide reduces neurodegeneration in vivo. J. Neurosci. 33, 334-343.
105. Takahashi, S., Saito, T., Hisanaga, S., Pant, H. C. and Kulkarni, A. B. (2003). Tau phosphorylation by cyclin-dependent kinase 5/p39 during brain development reduces its affinity for microtubules. J. Biol. Chem. 278, 10506-10515.
106. Tandon, A., Yu, H., Wang, L., Rogaeva, E., Sato, C., Chishti, M. A., Kawarai, T., Hasegawa, H., Chen, F., Davies, P. et al. (2003). Brain levels of CDK5 activator p25 are not increased in Alzheimer's or other neurodegenerative diseases with neurofibrillary tangles. J. Neurochem. 86, 572-581.
107. Tang, D., Yeung, J., Lee, K. Y., Matsushita, M., Matsui, H., Tomizawa, K., Hatase, O., Wang, J. H. (1995). An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator. J. Biol. Chem. 270, 26897-26903.
108. Tang, D., Chun, A. C., Zhang, M. and Wang, J. H. (1997). Cyclin-dependent kinase 5 (Cdk5) activation domain of neuronal Cdk5 activator. Evidence of the existence of cyclin fold in neuronal Cdk5a activator. J. Biol. Chem. 272, 12318-12327.
109. Taniguchi, S., Fujita, Y., Hayashi, S., Kakita, A., Takahashi, H., Murayama, S., Saido, T. C., Hisanaga, S., Iwatsubo, T. and Hasegawa, M. (2001). Calpainmediated degradation of p35 to p25 in postmortem human and rat brains. FEBS Lett. 489, 46-50.
110. Tarricone, C., Dhavan, R., Peng, J., Areces, L. B., Tsai, L. H. and Musacchio, A. (2001). Structure and regulation of the CDK5-p25(nck5a) complex. Mol. Cell 8, 657-669.
111. Tsai, L. H., Harlow, E. and Meyerson, M. (1991). Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Nature 353, 174-177.
112. Tsai, L. H., Lees, E., Faha, B., Harlow, E. and Riabowol, K. (1993). The cdk2 kinase is required for the G1-to-S transition in mammalian cells. Oncogene 8, 1593-1602.
113. Tsai, L. H., Delalle, I., Caviness, V. S., Jr, Chae, T. and Harlow, E. (1994). p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 371, 419-423.
114. Tseng, H. C., Zhou, Y., Shen, Y. and Tsai, L. H. (2002). A survey of Cdk5 activator p35 and p25 levels in Alzheimer's disease brains. FEBS Lett. 523, 58-62.
115. Utreras, E., Futatsugi, A., Rudrabhatla, P., Keller, J., Iadarola, M. J., Pant, H. C. and Kulkarni, A. B. (2009). Tumor necrosis factor-alpha regulates cyclin-dependent kinase 5 activity during pain signaling through transcriptional activation of p35. J. Biol. Chem. 284, 2275-2284.
116. Wei, F. Y., Tomizawa, K., Ohshima, T., Asada, A., Saito, T., Nguyen, C., Bibb, J. A., Ishiguro, K., Kulkarni, A. B., Pant, H. C. et al. (2005). Control of cyclin-dependent kinase 5 (Cdk5) activity by glutamatergic regulation of p35 stability. J. Neurochem. 93, 502-512.
117. Wen, Y., Yu,W. H., Maloney, B., Bailey, J., Ma, J., Marié, I., Maurin, T.,Wang, L., Figueroa, H., Herman, M. et al. (2008). Transcriptional regulation of betasecretase by p25/cdk5 leads to enhanced amyloidogenic processing. Neuron 57, 680-690.
118. Wong, A. S., Lee, R. H., Cheung, A. Y., Yeung, P. K., Chung, S. K., Cheung, Z. H. and Ip, N. Y. (2011). Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease. Nat. Cell Biol. 13, 568-579.
119. Xiong, Y., Zhang, H. and Beach, D. (1992). D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell 71, 505-514.
120. Yamada, M., Saito, T., Sato, Y., Kawai, Y., Sekigawa, A., Hamazumi, Y., Asada, A., Wada, M., Doi, H. and Hisanaga, S. (2007). Cdk5-p39 is a labile complex with the similar substrate specificity to Cdk5-p35. J. Neurochem. 102, 1477-1487.
121. Yamak, A., Latinkic, B. V., Dali, R., Temsah, R. and Nemer, M. (2014). Cyclin D2 is a GATA4 cofactor in cardiogenesis. Proc. Natl. Acad. Sci. USA 111, 1415-1420.
122. Yang, Y. R., He, Y., Zhang, Y., Li, Y., Li, Y., Han, Y., Zhu, H. and Wang, Y. (2007). Activation of cyclin-dependent kinase 5 (Cdk5) in primary sensory and dorsal horn neurons by peripheral inflammation contributes to heat hyperalgesia. Pain 127, 109-120.
123. Yoo, B. C. and Lubec, G. (2001). p25 protein in neurodegeneration. Nature 411, 763-764, discussion 764-765.
124. Zhang, P., Yu, P. C., Tsang, A. H., Chen, Y., Fu, A. K., Fu, W. Y., Chung, K. K. and Ip, N. Y. (2010). S-nitrosylation of cyclin-dependent kinase 5 (cdk5) regulates its kinase activity and dendrite growth during neuronal development. J. Neurosci. 30, 14366-14370.
125. Zhang, L., Liu, W., Szumlinski, K. K. and Lew, J. (2012). p10, the N-terminal domain of p35, protects against CDK5/p25-induced neurotoxicity. Proc. Natl. Acad. Sci. USA 109, 20041-20046.
126. Zheng, M., Leung, C. L. and Liem, R. K. (1998). Region-specific expression of cyclin-dependent kinase 5 (cdk5) and its activators, p35 and p39, in the developing and adult rat central nervous system. J. Neurobiol. 35, 141-159.
127. Zheng, Y. L., Li, B. S., Amin, N. D., Albers, W. and Pant, H. C. (2002). A peptide derived from cyclin-dependent kinase activator (p35) specifically inhibits Cdk5 activity and phosphorylation of tau protein in transfected cells. Eur. J. Biochem. 269, 4427-4434.
128. Zhu, J. H., Guo, F., Shelburne, J., Watkins, S. and Chu, C. T. (2003). Localization of phosphorylated ERK/MAP kinases to mitochondria and autophagosomes in Lewy body diseases. Brain Pathol. 13, 473-481.
129. Zukerberg, L. R., Patrick, G. N., Nikolic, M., Humbert, S., Wu, C. L., Lanier, L. M., Gertler, F. B., Vidal, M., Van Etten, R. A. and Tsai, L. H. (2000). Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth. Neuron 26, 633-646.