Interplay between the p53 tumor suppressor protein family and Cdk5: Novel therapeutic approaches for the treatment of neurodegenerative diseases using selective Cdk inhibitors

Molecular Neurobiology

Volumn 34, Issue 1, 2006, Pages 27-49

  Schmid, Gerald ^a,b   Strosznajder, Joanna B ^c   Wesierska Gadek, Józefa ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^c POLISH ACADEMY OF SCIENCES   (Poland)

Author keywords

Apoptosis; Cdk inhibitors; Cell cycle arrest

Indexed keywords

CYCLIN DEPENDENT KINASE 5; PROTEIN P53; TUMOR SUPPRESSOR PROTEIN;

CELL ACTIVATION; CELL ADHESION; CELL CYCLE; CELL DIFFERENTIATION; CELL MOTILITY; CELL PROLIFERATION; CYTOSKELETON; DOWN REGULATION; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME REGULATION; HUMAN; MITOSIS; NEUROFILAMENT; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FAMILY; REVIEW;

EID: 33749057073     PISSN: 08937648     EISSN: None     Source Type: Journal    
DOI: 10.1385/MN:34:1:27     Document Type: Review

References (169)

1. Sherr C. J. and Roberts J. M. (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 13, 1501-1512.
2. Giovanni A., Wirtz-Brugger F., Keramaris E., Slack R., and Park D. S. (1999) Involvement of cell cycle elements, cyclin-dependent kinases, pRb, and E2F x DP, in B-amyloid-induced neuronal death. J. Biol. Chem. 274, 19,011-19,016.
3. Yang Y., Geldmacher D. S., and Herrup K. (2001) DNA replication precedes neuronal cell death in Alzheimer's disease. J. Neurosci. 21, 2661-2668.
4. Yang Y., Mufson E. J., and Herrup K. (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease. J. Neurosci. 23, 2557-2563.
5. Hayes T. E., Valtz N. L., and McKay R. D. (1991) Downregulation of CDC2 upon terminal differentiation of neurons. New Biol. 3, 259-269.
6. Okano H. J., Pfaff D. W., and Gibbs R. B. (1993) RB and Cdc2 expression in brain: correlations with 3H-thymidine incorporation and neurogenesis. J. Neurosci. 13, 2930-2938.
7. van Grunsven L. A., Thomas A., Urdiales J. L., et al. (1996) Nerve growth factor-induced accumulation of PC12 cells expressing cyclin D1: evidence for a G1 phase block. Oncogene 12, 855-862.
8. Yan G. Z. and Ziff E. B. (1995) NGF regulates the PC12 cell cycle machinery through specific inhibition of the Cdk kinases and induction of cyclin D1. J. Neurosci. 15, 6200-6212.
9. Sicinski P., Donaher J. L., Parker S. B., et al. (1995) Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82, 621-630.
10. Xiong W., Pestell R., and Rosner M. R. (1997) Role of cyclins in neuronal differentiation of immortalized hippocampal cells. Mol. Cell. Biol. 17, 6585-6597.
11. Nguyen M. D., Mushynski W. E., and Julien J. P. (2002) Cycling at the interface between neurodevelopment and neurodegeneration. Cell Death Differ. 9, 1294-1306.
12. O'Hare M., Wang F., and Park D. S. (2002) Cyclin-dependent kinases as potential targets to improve stroke outcome. Pharmacol. Ther. 93, 135-143.
13. Dhavan R. and Tsai L. H. (2001) A decade of CDK5. Nat. Rev. Mol. Cell Biol. 2, 749-759.
14. Nikolic M., Dudek H., Kwon Y. T., Ramos Y. F., and Tsai L. H. (1996) The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation. Genes Dev. 10, 816-825.
15. 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.
16. 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.
17. Qi Z., Huang Q. Q., Lee K. Y., Lew J., and Wang J. H. (1995) Reconstitution of neuronal Cdc2-like kinase from bacteria-expressed Cdk5 and an active fragment of the brain-specific activator. Kinase activation in the absence of Cdk5 phosphorylation. J. Biol. Chem. 270, 10,847-10,854.
18. Ishiguro K., Kobayashi S., Omori A., et al. (1994) Identification of the 23 kDa subunit of tau protein kinase II as a putative activator of cdk5 in bovine brain. FEBS Lett. 342, 203-208.
19. Lew J., Huang Q. Q., Qi Z., et al. H. (1994) A brain-specific activator of cyclin-dependent kinase 5. Nature 371, 423-426.
20. Brown N. R., Noble M. E., Endicott J. A., et al. (1995) The crystal structure of cyclin A. Structure 3, 1235-1247.
21. 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, 12,318-12,327.
22. 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.
23. 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.
24. Chae T., Kwon Y. T., Bronson R., Dikkes P., Li E., and Tsai L. H. (1997) Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 18, 29-42.
25. Kwon Y. T. and Tsai L. H. (1998) A novel disruption of cortical development in p35(-/-) mice distinct from reeler. J. Comp. Neurol. 395, 510-522.
26. Kwon Y. T., Tsai L. H., and Crandall J. E. (1999) Callosal axon guidance defects in p35(-/-) mice. J. Comp. Neurol. 415, 218-229.
27. Nikolic M., Chou M. M., Lu W., Mayer B. J., and Tsai L. H. (1998) The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity. Nature 395, 194-198.
28. Patrick G. N., Zhou P., Kwon Y. T., Howley P. M., and Tsai L. H. (1998) p35, the neuronal-specific activator of cyclin-dependent kinase 5 (Cdk5) is degraded by the ubiquitin-proteasome pathway. J. Biol. Chem. 273, 24,057-24,064.
29. Tang D., Yeung J., Lee K. Y., et al. (1995) An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator. J. Biol. Chem. 270, 26,897-26,903.
30. Beaudette K. N., Lew J., and Wang J. H. (1993) Substrate specificity characterization of a cdc2-like protein kinase purified from bovine brain. J. Biol. Chem. 268, 20,825-20,830.
31. Songyang Z., Lu K. P., Kwon Y. T., et al. (1996) A structural basis for substrate specificities of protein Ser/Thr kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk1. Mol. Cell. Biol. 16, 6486-6493.
32. Lee K. Y., Qi Z., Yu Y. P., and Wang J. H. (1997) Neuronal Cdc2-like kinases: neuron-specific forms of Cdk5. Int. J. Biochem. Cell Biol. 29, 951-958.
33. Matsubara M., Kusubata M., Ishiguro K., Uchida T., Titani K., and Taniguchi H. (1996) Site-specific phosphorylation of synapsin I by mitogen-activated protein kinase and Cdk5 and its effects on physiological functions. J. Biol. Chem. 271, 21,108-21,113.
34. Shuang R., Zhang L., Fletcher A., Groblewski G. E., Pevsner J., and Stuenkel E. L. (1998) Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings. J. Biol. Chem. 273, 4957-4966.
35. Li B. S., Sun M. K., Zhang L., et al. (2001) Regulation of NMDA receptors by cyclin-dependent kinase-5. Proc. Natl. Acad. Sci. USA 98, 12,742-12,747.
36. Nakanishi S. (1992) Molecular diversity of glutamate receptors and implications for brain function. Science 258, 597-603.
37. Tsai L. H., Takahashi T., Caviness V. S. Jr., and Harlow E. (1993) Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic mouse nervous system. Development 119, 1029-1040.
38. el-Deiry W. S., Tokino T., Velculescu V. E., et al. (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817-825.
39. Yonish-Rouach E., Resnitzky D., Lotem J., Sachs L., Kimchi A., and Oren M. (1991) Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352, 345-347.
40. Atadja P., Wong H., Garkavtsev I., Veillette C., and Riabowol K. (1995) Increased activity of p53 in senescing fibroblasts. Proc. Natl. Acad. Sci. USA 92, 8348-8352.
41. Itahana K., Dimri G. P., Hara E., et al. (2002) A role for p53 in maintaining and establishing the quiescence growth arrest in human cells. J. Biol. Chem. 277, 18,206-18,214.
42. Wesierska-Gadek J., Ranftler C., and Schmid G. (2005) Physiological ageing: role of p53 and PARP-1 tumor suppressors in the regulation of terminal senescence. J. Physiol. Pharmacol. 56(Suppl 2), 77-88.
43. Wesierska-Gadek J., Wojciechowski J., Ranftler C., and Schmid G. (2005) Role of p53 tumor suppressor in ageing: regulation of transient cell cycle arrest and terminal senescence. J. Physiol. Pharmacol. 56, 15-28.
44. Pozniak C. D., Radinovic S., Yang A., McKeon F., Kaplan D. R., and Miller F. D. (2000) An anti-apoptotic role for the p53 family member, p73, during developmental neuron death. Science 289, 304-306.
45. Armstrong J. F., Kaufman M. H., Harrison D. J., and Clarke A. R. (1995) High-frequency developmental abnormalities in p53-deficient mice. Curr. Biol. 5, 931-936.
46. Cecconi F., Alvarez-Bolado G., Meyer B. I., Roth K. A., and Gruss P. (1998) Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell 94, 727-737.
47. Kuida K., Haydar T. F., Kuan C. Y., et al. (1998) Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94, 325-337.
48. Kuida K., Zheng T. S., Na S., et al. (1996) Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384, 368-372.
49. Sah V. P., Attardi L. D., Mulligan G. J., Williams B. O., Bronson R. T., and Jacks T. (1995) A subset of p53-deficient embryos exhibit exencephaly. Nat. Genet. 10, 175-180.
50. Yoshida H., Kong Y. Y., Yoshida R., et al. (1998) Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell 94, 739-750.
51. Cregan S. P., MacLaurin J. G., Craig C. G., et al. (1999) Bax-dependent caspase-3 activation is a key determinant in p53-induced apoptosis in neurons. J. Neurosci. 19, 7860-7869.
52. Crumrine R. C., Thomas A. L., and Morgan P. F. (1994) Attenuation of p53 expression protects against focal ischemic damage in transgenic mice. J. Cereb. Blood Flow Metab. 14, 887-891.
53. Yang X., Klein R., Tian X., Cheng H. T., Kopan R., and Shen J. (2004) Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway. Dev. Biol. 269, 81-94.
54. Artavanis-Tsakonas S., Rand M. D., and Lake R. J. (1999) Notch signaling: cell fate control and signal integration in development. Science 284, 770-776.
55. Brou C., Logeat F., Gupta N., et al. (2000) A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol. Cell 5, 207-216.
56. Mumm J. S., Schroeter E. H., Saxena M. T., et al. (2000) Aligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Mol. Cell 5, 197-206.
57. Schroeter E. H., Kisslinger J. A., and Kopan R. (1998) Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393, 382-386.
58. Chambers C. B., Peng Y., Nguyen H., Gaiano N., Fishell G., and Nye J. S. (2001) Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors. Development 128, 689-702.
59. Morimura T., Goitsuka R., Zhang Y., Saito I., Reth M., and Kitamura D. (2000) Cell cycle arrest and apoptosis induced by Notch1 in B cells. J. Biol. Chem. 275, 36,523-36,531.
60. Deftos M. L., He Y. W., Ojala E. W., and Bevan M. J. (1998) Correlating notch signaling with thymocyte maturation. Immunity 9, 777-786.
61. Love S. (2003) Apoptosis and brain ischaemia. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 267-282.
62. Yu S. W., Wang H., Dawson T. M., and Dawson V. L. (2003) Poly(ADP-ribose) polymerase-1 and apoptosis inducing factor in neurotoxicity. Neurobiol. Dis. 14, 303-317.
63. Yu S. W., Wang H., Poitras M. F., et al. (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297, 259-263.
64. Cao G., Pei W., Lan J., et al. (2001) Caspase-activated DNase/DNA fragmentation factor 40 mediates apoptotic DNA fragmentation in transient cerebral ischemia and in neuronal cultures. J. Neurosci. 21, 4678-4690.
65. Gillardon F., Bottiger B., Schmitz B., Zimmermann M., and Hossmann K. A. (1997) Activation of CPP-32 protease in hippocampal neurons following ischemia and epilepsy. Brain Res. Mol. Brain Res. 50, 16-22.
66. Hermann D. M., Kilic E., Hata R., Hossmann K. A., and Mies G. (2001) Relationship between metabolic dysfunctions, gene responses and delayed cell death after mild focal cerebral ischemia in mice. Neuroscience 104, 947-955.
67. Namura S., Zhu J., Fink K., et al. (1998) Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J. Neurosci. 18, 3659-3668.
68. MacManus J. P. and Buchan A. M. (2000) Apoptosis after experimental stroke: fact or fashion? J. Neurotrauma 17, 899-914.
69. Martin L. J., Al-Abdulla N. A., Brambrink A. M., Kirsch J. R., Sieber F. E., and Portera-Cailliau C. (1998) Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: A perspective on the contributions of apoptosis and necrosis. Brain Res. Bull. 46, 281-309.
70. Nicotera P. and Lipton S. A. (1999) Excitotoxins in neuronal apoptosis and necrosis. J. Cereb. Blood Flow Metab. 19, 583-591.
71. Strosznajder R. P., Jesko H., Banasik M., and Tanaka S. (2005) Effects of p53 inhibitor on survival and death of cells subjected to oxidative stress. J. Physiol. Pharmacol. 56(Suppl 4), 215-221.
72. de la Monte S. M., Sohn Y. K., and Wands J. R. (1997) Correlates of p53- and Fas (CD95)-mediated apoptosis in Alzheimer's disease. J. Neurol. Sci. 152, 73-83.
73. Ohyagi Y., Asahara H., Chui D. H., et al. (2005) Intracellular Abeta42 activates p53 promoter: a pathway to neurodegeneration in Alzheimer's disease. FASEB J. 19, 255-257.
74. Kitamura Y., Shimohama S., Kamoshima W., Matsuoka Y., Nomura Y., and Taniguchi T. (1997) Changes of p53 in the brains of patients with Alzheimer's disease. Biochem. Biophys. Res. Commun. 232, 418-421.
75. Chung Y. H., Shin C., Kim M. J., Lee B., Park K. H., and Cha C. I. (2000) Immunocytochemical study on the distribution of p53 in the hippocampus and cerebellum of the aged rat. Brain Res. 885, 137-141.
76. Barlow C., Dennery P. A., Shigenaga M. K., et al. (1999) Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs. Proc. Natl. Acad. Sci. USA 96, 9915-9919.
77. Nakaso K., Kitayama M., Fukuda H., et al. (2000) Oxidative stress-related proteins A170 and heme oxygenase-1 are differently induced in the rat cerebellum under kainate-mediated excitotoxicity. Neurosci. Lett. 282, 57-60.
78. Nicholson D. W. (2000) From bench to clinic with apoptosis-based therapeutic agents. Nature 407, 810-816.
79. Tamm I., Schriever F., and Dorken B. (2001) Apoptosis: implications of basic research for clinical oncology. Lancet Oncol. 2, 33-42.
80. Slack R. S., Belliveau D. J., Rosenberg M., et al. (1996) Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons. J. Cell Biol. 135, 1085-1096.
81. Xu X., Yang D., Wyss-Coray T., et al. (1999) Wild-type but not Alzheimer-mutant amyloid precursor protein confers resistance against p53-mediated apoptosis. Proc. Natl. Acad. Sci. USA 96, 7547-7552.
82. Bellamy C. O., Clarke A. R., Wyllie A. H., and Harrison D. J. (1997) p53 Deficiency in liver reduces local control of survival and proliferation, but does not affect apoptosis after DNA damage. FASEB J. 11, 591-599.
83. Morrison R. S., Wenzel H. J., Kinoshita Y., Robbins C. A., Donehower L. A., and Schwartzkroin P. A. (1996) Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death. J. Neurosci. 16, 1337-1345.
84. Oda E., Ohki R., Murasawa H., et al. (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288, 1053-1058.
85. Attardi L. D., Reczek E. E., Cosmas C., et al. (2000) PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes Dev. 14, 704-718.
86. Koumenis C., Alarcon R., Hammond E., et al. (2001) Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol. Cell. Biol. 21, 1297-1310.
87. Nakade K., Zheng H., Ganguli G., Buchwalter G., Gross C., and Wasylyk B. (2004) The tumor suppressor p53 inhibits Net, an effector of Ras/extracellular signal-regulated kinase signaling. Mol. Cell. Biol. 24, 1132-1142.
88. Seto E., Usheva A., Zambetti G. P., et al. (1992) Wild-type p53 binds to the TATA-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA 89, 12,028-12,032.
89. Miyashita T., Harigai M., Hanada M., and Reed J. C. (1994) Identification of a p53-dependent negative response element in the bcl-2 gene. Cancer Res. 54, 3131-3135.
90. Cregan S. P., Arbour N. A., Maclaurin J. G., et al. (2004) p53 activation domain 1 is essential for PUMA upregulation and p53-mediated neuronal cell death. J. Neurosci. 24, 10,003-10,012.
91. Zhu J., Zhang S., Jiang J., and Chen X. (2000) Definition of the p53 functional domains necessary for inducing apoptosis. J. Biol. Chem. 275, 39,927-39,934.
92. Huang D. C. and Strasser A. (2000) BH3-Only proteins-essential initiators of apoptotic cell death. Cell 103, 839-842.
93. Puthalakath H. and Strasser A. (2002) Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins. Cell Death Differ. 9, 505-512.
94. Melino G., Bernassola F., Ranalli M., et al. (2004) p73 Induces apoptosis via PUMA transactivation and Bax mitochondrial translocation. J. Biol. Chem. 279, 8076-8083.
95. Hershko T. and Ginsberg D. (2004) Up-regulation of Bcl-2 homology 3 (BH3)-only proteins by E2F1 mediates apoptosis. J. Biol. Chem. 279, 8627-8634.
96. Bonini P., Cicconi S., Cardinale A., et al. (2004) Oxidative stress induces p53-mediated apoptosis in glia: p53 transcription-independent way to die. J. Neurosci. Res. 75, 83-95.
97. Caelles C., Helmberg A., and Karin M. (1994) p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature 370, 220-223.
98. Haupt Y., Rowan S., Shaulian E., Vousden K. H., and Oren M. (1995) Induction of apoptosis in HeLa cells by trans-activation-deficient p53. Genes Dev. 9, 2170-2183.
99. Zhu J., Jiang J., Zhou W., Zhu K., and Chen X. (1999) Differential regulation of cellular target genes by p53 devoid of the PXXP motifs with impaired apoptotic activity. Oncogene 18, 2149-2155.
100. Charlot J. F., Pretet J. L., Haughey C., and Mougin C. (2004) Mitochondrial translocation of p53 and mitochondrial membrane potential (Delta Psi m) dissipation are early events in staurosporine-induced apoptosis of wild type and mutated p53 epithelial cells. Apoptosis 9, 333-343.
101. Chipuk J. E., Maurer U., Green D. R., and Schuler M. (2003) Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer Cell 4, 371-381.
102. Mihara M., Erster S., Zaika A., et al. (2003) p53 has a direct apoptogenic role at the mitochondria. Mol. Cell 11, 577-590.
103. Chipuk J. E., Kuwana T., Bouchier-Hayes L., et al. (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303, 1010-1014.
104. Marchenko N. D., Zaika A., and Moll U. M. (2000) Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J. Biol. Chem. 275, 16,202-16,212.
105. Ding H. F., McGill G., Rowan S., Schmaltz C., Shimamura A., and Fisher D. E. (1998) Oncogene-dependent regulation of caspase activation by p53 protein in a cell-free system. J. Biol. Chem. 273, 28,378-28,383.
106. Johnson M. D., Kinoshita Y., Xiang H., Ghatan S., and Morrison R. S. (1999) Contribution of p53-dependent caspase activation to neuronal cell death declines with neuronal maturation. J. Neurosci. 19, 2996-3006.
107. Matsuda K., Yoshida K., Taya Y., Nakamura K., Nakamura Y., and Arakawa H. (2002) p53AIP1 regulates the mitochondrial apoptotic pathway. Cancer Res. 62, 2883-2889.
108. Yoshida K., Monden M., Nakamura Y., and Arakawa H. (2004) Adenovirus-mediated p53AIP1 gene transfer as a new strategy for treatment of p53-resistant tumors. Cancer Sci. 95, 91-97.
109. Wesierska-Gadek J., Gueorguieva M., and Horky M. (2005) Roscovitine-induced up-regulation of p53AIP1 protein precedes the onset of apoptosis in human MCF-7 breast cancer cells. Mol. Cancer Ther. 4, 113-124.
110. Zhang J., Krishnamurthy P. K., and Johnson G. V. (2002) Cdk5 phosphorylates p53 and regulates its activity. J. Neurochem. 81, 307-313.
111. Courtois S., Verhaegh G., North S., et al. (2002) DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53. Oncogene 21, 6722-6728.
112. Yang A., Kaghad M., Wang Y., et al. (1998) p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol. Cell 2, 305-316.
113. Casciano I., Ponzoni M., Cunsolo C., Tonini G., and Romani M. (1999) Different p73 splicing variants are expressed in distinct tumour areas of a multifocal neuroblastoma. Cell Death Differ. 6, 391-393.
114. De Laurenzi V., Costanzo A., Barcaroli D., et al. (1998) Two new p73 splice variants, gamma and delta, with different transcriptional activity. J. Exp. Med. 188, 1763-1768.
115. De Laurenzi V. D., Catani M. V., Terrinoni A., et al. (1999) Additional complexity in p73: induction by mitogens in lymphoid cells and identification of two new splicing variants epsilon and zeta. Cell Death Differ. 6, 389,390.
116. Kong X. T., Valentine V. A., Rowe S. T., et al. (1999) Lack of homozygously inactivated p73 in single-copy MYCN primary neuroblastomas and neuroblastoma cell lines. Neoplasia 1, 80-89.
117. Jost C. A., Marin M. C., and Kaelin W. G. Jr. (1997) p73 is a human p53-related protein that can induce apoptosis [see comments]. Nature 389, 191-194.
118. Kaghad M., Bonnet H., Yang A., et al. (1997) Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90, 809-819.
119. Donehower L. A. and Bradley A. (1993) The tumor suppressor p53. Biochim. Biophys. Acta 1155, 181-205.
120. DeLeo A. B., Jay G., Appella E., Dubois G. C., Law L. W., and Old L. J. (1979) Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc. Natl. Acad. Sci. USA 76, 2420-2424.
121. Lane D. P. and Crawford L. V. (1979) T antigen is bound to a host protein in SV40-transformed cells. Nature 278, 261-263.
122. Linzer D. I. and Levine A. J. (1979) Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17, 43-52.
123. Flores E. R., Tsai K. Y., Crowley D., et al. (2002) p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature 416, 560-564.
124. Urist M. and Prives C. (2002) p53 leans on its siblings. Cancer Cell 1, 311-313.
125. Levine A. J. (1997) p53, the cellular gatekeeper for growth and division. Cell 88, 323-331.
126. Irwin M. S. and Kaelin W. G. (2001) p53 family update: p73 and p63 develop their own identities. Cell Growth Differ. 12, 337-349.
127. Yang A., Walker N., Bronson R., et al. (2000) p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature 404, 99-103.
128. Mills A. A., Zheng B., Wang X. J., Vogel H., Roop D. R., and Bradley A. (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398, 708-713.
129. Yang A., Schweitzer R., Sun D., et al. (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398, 714-718.
130. Wood K. A., Dipasquale B., and Youle R. J. (1993) In situ labeling of granule cells for apoptosis-associated DNA fragmentation reveals different mechanisms of cell loss in developing cerebellum. Neuron 11, 621-632.
131. Beilharz E. J., Williams C. E., Dragunow M., Sirimanne E. S., and Gluckman P. D. (1995) Mechanisms of delayed cell death following hypoxic-ischemic injury in the immature rat: evidence for apoptosis during selective neuronal loss. Brain Res. Mol. Brain Res. 29, 1-14.
132. Friedman J. E. and Haddad G. G. (1993) Major differences in Ca2+i response to anoxia between neonatal and adult rat CA1 neurons: role of Ca2+o and Na+o. J. Neurosci. 13, 63-72.
133. Hill I. E., MacManus J. P., Rasquinha I., and Tuor U. I. (1995) DNA fragmentation indicative of apoptosis following unilateral cerebral hypoxia-ischemia in the neonatal rat. Brain Res. 676, 398-403.
134. Mehmet H., Yue X., Squier M. V., et al. (1994) Increased apoptosis in the cingulate sulcus of newborn piglets following transient hypoxia-ischaemia is related to the degree of high energy phosphate depletion during the insult. Neurosci. Lett. 181, 121-125.
135. Pittman R. N., Wang S., DiBenedetto A. J., and Mills J. C. (1993) A system for characterizing cellular and molecular events in programmed neuronal cell death. J. Neurosci. 13, 3669-3680.
136. Chandel N. S. and Schumacker P. T. (2000) Cellular oxygen sensing by mitochondria: old questions, new insight. J. Appl. Physiol. 88, 1880-1889.
137. Chandel N. S., Budinger G. R., Choe S. H., and Schumacker P. T. (1997) Cellular respiration during hypoxia. Role of cytochrome oxidase as the oxygen sensor in hepatocytes. J. Biol. Chem. 272, 18,808-18,816.
138. Semenza G. L. and Wang G. L. (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell. Biol. 12, 5447-5454.
139. An W. G., Kanekal M., Simon M. C., Maltepe E., Blagosklonny M. V., and Neckers L. M. (1998) Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature 392, 405-408.
140. Blagosklonny M. V., An W. G., Romanova L. Y., Trepel J., Fojo T., and Neckers L. (1998) p53 inhibits hypoxia-inducible factor-stimulated transcription. J. Biol. Chem. 273, 11,995-11,998.
141. Chen J., Nagayama T., Jin K., et al. (1998) Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. J. Neurosci. 18, 4914-4928.
142. Love S., Barber R., Srinivasan A., and Wilcock G. K. (2000) Activation of caspase-3 in permanent and transient brain ischaemia in man. Neuroreport 11, 2495-2499.
143. Leker R. R., Aharonowiz M., Greig N. H., and Ovadia H. (2004) The role of p53-induced apoptosis in cerebral ischemia: effects of the p53 inhibitor pifithrin alpha. Exp. Neurol. 187, 478-486.
144. Xiang H., Hochman D. W., Saya H., Fujiwara T., Schwartzkroin P. A., and Morrison R. S. (1996) Evidence for p53-mediated modulation of neuronal viability. J. Neurosci. 16, 6753-6765.
145. Oppenheim R. W. (1991) Cell death during development of the nervous system. Annu. Rev. Neurosci. 14, 453-501.
146. Miller F. D., Pozniak C. D., and Walsh G. S. (2000) Neuronal life and death: an essential role for the p53 family. Cell Death Differ. 7, 880-888.
147. Morrison R. S., Kinoshita Y., Johnson M. D., Guo W., and Garden G. A. (2003) p53-dependent cell death signaling in neurons. Neurochem. Res. 28, 15-27.
148. Jacobs W. B., Walsh G. S., and Miller F. D. (2004) Neuronal survival and p73/p63/p53: a family affair. Neuroscientist 10, 443-455.
149. Pozniak C. D., Barnabe-Heider F., Rymar V. V., Lee A. F., Sadikot A. F., and Miller F. D. (2002) p73 is required for survival and maintenance of CNS neurons. J. Neurosci. 22, 9800-9809.
150. Kaplan D. R. and Miller F. D. (2000) Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 10, 381-391.
151. Lee A. F., Ho D. K., Zanassi P., Walsh G. S., Kaplan D. R., and Miller F. D. (2004) Evidence that DeltaNp73 promotes neuronal survival by p53-dependent and p53-independent mechanisms. J. Neurosci. 24, 9174-9184.
152. Cheng T., Liu D., Griffin J. H., et al. (2003) Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat. Med. 9, 338-342.
153. Zhu X., Yu Q. S., Cutler R. G., et al. (2002) Novel p53 inactivators with neuroprotective action: syntheses and pharmacological evaluation of 2-imino-2,3,4,5,6,7-hexahydrobenzothiazole and 2-imino-2,3,4,5,6,7- hexahydrobenzoxazole derivatives. J. Med. Chem. 45, 5090-5097.
154. Virag L. and Szabo C. (2002) The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol. Rev. 54, 375-429.
155. Monaco E. A. 3rd (2004) Recent evidence regarding a role for Cdk5 dysregulation in Alzheimer's disease. Curr. Alzheimer Res. 1, 33-38.
156. Tsai L. H., Lee M. S., and Cruz J. (2004) Cdk5, a therapeutic target for Alzheimer's disease? Biochim. Biophys. Acta 1697, 137-142.
157. Fischer P. M. and Gianella-Borradori A. (2005) Recent progress in the discovery and development of cyclin-dependent kinase inhibitors. Expert Opin. Investig. Drugs 14, 457-477.
158. Wesierska-Gadek J. and Schmid G. (2006) Dual action of the inhibitors of cyclin-dependent kinases (CDKs): targeting of the cell cycle progression and activation of wt p53 protein. Expert. Opin. Investig. Drugs 15, 23-38.
159. de la Motte S. and Gianella-Borradori A. (2004) Pharmacokinetic model of R-roscovitine and its metabolite in healthy male subjects. Int. J. Clin. Pharmacol. Ther. 42, 232-239.
160. McClue S. J., Blake D., Clarke R., et al. (2002) In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine). Int. J. Cancer 102, 463-468.
161. Alvarez A., Toro R., Caceres A., and Maccioni R. B. (1999) Inhibition of tau phosphorylating protein kinase cdk5 prevents beta-amyloid-induced neuronal death. FEBS Lett. 459, 421-426.
162. Maas J. W. Jr., Horstmann S., Borasio G. D., Anneser J. M., Shooter E. M., and Kahle P. J. (1998) Apoptosis of central and peripheral neurons can be prevented with cyclin-dependent kinase/mitogen-activated protein kinase inhibitors. J. Neurochem. 70, 1401-1410.
163. Kitagawa M., Okabe T., Ogino H., et al. (1993) Butyrolactone I, a selective inhibitor of cdk2 and cdc2 kinase. Oncogene 8, 2425-2432.
164. Johnson K., Liu L., Majdzadeh N., et al. (2005) Inhibition of neuronal apoptosis by the cyclin-dependent kinase inhibitor GW8510: identification of 3′ substituted indolones as a scaffold for the development of neuroprotective drugs. J. Neurochem. 93, 538-548.
165. Weishaupt J. H., Kussmaul L., Grotsch P., et al. (2003) Inhibition of CDK5 is protective in necrotic and apoptotic paradigms of neuronal cell death and prevents mitochondrial dysfunction. Mol. Cell. Neurosci. 24, 489-502.
166. Gillardon F., Steinlein P., Burger E., Hildebrandt T., and Gerner C. (2005) Phosphoproteome and transcriptome analysis of the neuronal response to a CDK5 inhibitor. Proteomics 5, 1299-1307.
167. Gillardon F., Schrattenholz A., and Sommer B. (2005) Investigating the neuroprotective mechanism of action of a CDK5 inhibitor by phosphoproteome analysis. J. Cell. Biochem. 95, 817-826.
168. Potterat O., Puder C., Bolek W., et al. (2005) Clausine Z, a new carbazole alkaloid from Clausena excavata with inhibitory activity on CDK5. Pharmazie 60, 637-639.
169. Zapata-Torres G., Opazo F., Salgado C., et al. (2004) Effects of natural flavones and flavonols on the kinase activity of Cdk5. J. Nat. Prod. 67, 416-420.