臺灣博碩士論文加值系統

本研究的目的是想要探討DDA3對microtubule dynamics的調控以及如何影響與microtubule有關的功能。DDA3是本實驗室發現的一個p53的轉譯標地(transcriptional target)，DDA3在細胞中的分布情形與microtubule重疊，且能夠與microtubule plus end binding protein EB3結合。藉由螢光免疫染色分析和GST pull-down assay，定出在DDA3蛋白序列上與microtubule和EB3 的結合區域皆是amino acids 118-329。在細胞中表現DDA3能夠引起microtubule聚集成束(bundling)，這些成束的microtubule具有nocodazole抗性，並且發生acetylation。另外以in vitro MT bundling assay，在電子顯微鏡的觀察下，發現DDA3蛋白能夠直接使microtubule成束並使之穩定。DDA3在腦部有特異性表現，且此表現與p53無關。為了更進一步探討DDA3是否參與神經細胞的分化，以PC12 pheochromocytoma和N2a neuroblastoma的細胞來探討DDA3在神經突起(neurite)生成過程中可能扮演的角色。在NGF誘導PC12分化的過程中，表現DDA3能夠抑制neurite的生成，相反的，在N2a細胞中抑制DDA3的表現又會促進neurite的生成。與上述結果一致的是，利用retinoic acid誘使N2a細胞分化的過程中，細胞中DDA3的表現量也是逐漸下降的。與DDA3相反，在N2a細胞中抑制DDA3結合蛋白EB3的表現時，在Retinoid acid誘導下，細胞無法生成neurite。總結以上結果，DDA3能夠調控microtubule dynamics，並且在neuritogenesis過程中扮演一個新穎性的角色。

The aim of this study is to investigate the effects of DDA3 on microtubule (MT) dynamics and functions. DDA3 is a p53 transcriptional target shown to be colocalized with MT in cells and bind MT plus end binding protein EB3. By immunofluorescence analysis and GST pull-down assay, we have mapped the MT and EB3 binding domains of DDA3. Both of them are amino acids 118-329. Ectopic expression of DDA3 in cells induced nocodazole-resistant MT bundles characterized by acetylation; in vitro MT bundling assay followed by electron microscopy analysis demonstrated that DDA3 directly bundles and stabilizes MT. DDA3 is expressed in the brain in a p53-independent manner. To examine if DDA3 is involved in MT-mediated activities, we explored the role of DDA3 in neurite formation using PC12 pheochromocytoma and N2a neuroblastoma cells. Overexpression of DDA3 inhibited neurite formation during NGF-induced PC12 differentiation, in contrast, knockdown of DDA3 expression by small interference RNA resulted in neurite outgrowth in N2a cells. Consistent with these findings, DDA3 expression was down-regulated during retinoic acid induced N2a differentiation. Interestingly, blocking the expression of EB3 suppressed the neurite outgrowth during induced differentiation of N2a cells. Together this study uncovers a novel role of DDA3 in MT dynamics and MT-mediated functions such as neurite formation.

Abstract…………………………………………………….1
摘要………………………………………………………….2
序論………………………………………………………….3
研究動機……………………………………………………23
實驗材料與方法……………………………………………24
實驗結果……………………………………………………33
實驗討論……………………………………………………41
參考資料……………………………………………………50
附圖…………………………………………………………58
附錄一………………………………………………………75
附錄二………………………………………………………84

1. Lane, D. P. & Crawford, L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature 1979, 278:261-3.
2. Linzer, D. I. & Levine, A. J. Characterization of a 54K dalton cellular SV40 tumor
antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 1979, 17:43-52.
3. Prives, C. Signaling to p53: breaking the MDM2-p53 circuit. Cell 1998, 95:5-8.
4. Oren, M. Decision making by p53: life, death and cancer. Cell Death. Differ. 2003, 10:431-42.
5. Hollstein, M. et al. Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acids Res. 1994, 22:3551-5.
6. Levine, A. J. p53, the cellular gatekeeper for growth and division. Cell 1997, 88:323-31.
7. Vousden, K. H. p53: death star. Cell 2000, 103:691-4.
8. Vogelstein, B., Lane, D. & Levine, A. J. Surfing the p53 network. Nature 2000, 408:307-10.
9. Tang, P. P. & Wang, F. F. Induction of IW32 erythroleukemia cell differentiation by p53 is dependent on protein tyrosine phosphatase. Leukemia 2000, 14:1292-300.
10. Lo, P. K. et al. Identification of a novel mouse p53 target gene DDA3. Oncogene 1999, 18:7765-74.
11. Hsieh, S. C., Lo, P. K. & Wang, F. F. Mouse DDA3 gene is a direct transcriptional target of p53 and p73. Oncogene 2002, 21:3050-7.
12. Desai, A. & Mitchison, T. J. Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol. 1997, 13:83-117.
13. Amos, L. A. & Schlieper, D. Microtubules and maps. Adv. Protein Chem. 2005, 71:257-98.
14. Kirschner, M. & Mitchison, T. Beyond self-assembly: from microtubules to morphogenesis. Cell 1986, 45:329-42.
15. Mimori-Kiyosue, Y. & Tsukita, S. "Search-and-capture" of microtubules through plus-end-binding proteins (+TIPs). J. Biochem. (Tokyo) 2003, 134:321-6.
16. Schuyler, S. C. & Pellman, D. Search, capture and signal: games microtubules and centrosomes play. J. Cell Sci. 2001, 114:247-55.
17. Gundersen, G. G. Evolutionary conservation of microtubule-capture mechanisms. Nat. Rev. Mol. Cell Biol. 2002, 3:296-304.
18. Schuyler, S. C. & Pellman, D. Microtubule "plus-end-tracking proteins": The end is just the beginning. Cell 2001, 105:421-4.
19. Galjart, N. & Perez, F. A plus-end raft to control microtubule dynamics and function. Curr. Opin. Cell Biol. 2003, 15:48-53.
20. Carvalho, P., Tirnauer, J. S. & Pellman, D. Surfing on microtubule ends. Trends Cell Biol. 2003, 13:229-37.
21. Khodjakov, A., Copenagle, L., Gordon, M. B., Compton, D. A. & Kapoor, T. M. Minus-end capture of preformed kinetochore fibers contributes to spindle morphogenesis. J. Cell Biol. 2003, 160:671-83.
22. Maiato, H., Rieder, C. L. & Khodjakov, A. Kinetochore-driven formation of kinetochore fibers contributes to spindle assembly during animal mitosis. J. Cell Biol. 2004, 167:831-40.
23. Raftopoulou, M. & Hall, A. Cell migration: Rho GTPases lead the way. Dev. Biol. 2004, 265:23-32.
24. Watanabe, T., Noritake, J. & Kaibuchi, K. Regulation of microtubules in cell migration. Trends Cell Biol. 2005, 15:76-83.
25. Palazzo, A. F., Eng, C. H., Schlaepfer, D. D., Marcantonio, E. E. & Gundersen, G. G. Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling. Science 2004, 303:836-9.
26. Daub, H., Gevaert, K., Vandekerckhove, J., Sobel, A. & Hall, A. Rac/Cdc42 and p65PAK regulate the microtubule-destabilizing protein stathmin through phosphorylation at serine 16. J. Biol. Chem. 2001, 276:1677-80.
27. Wittmann, T., Bokoch, G. M. & Waterman-Storer, C. M. Regulation of microtubule destabilizing activity of Op18/stathmin downstream of Rac1. J. Biol. Chem. 2004, 279:6196-203.
28. Etienne-Manneville, S. & Hall, A. Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature 2003, 421:753-6.
29. Etienne-Manneville, S. & Hall, A. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell 2001, 106:489-98.
30. Ezratty, E. J., Partridge, M. A. & Gundersen, G. G. Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat. Cell Biol. 2005, 7:581-90.
31. Gundersen, G. G. & Bulinski, J. C. Selective stabilization of microtubules oriented toward the direction of cell migration. Proc. Natl. Acad. Sci. U. S. A. 1988, 85:5946-50.
32. Gundersen, G. G., Khawaja, S. & Bulinski, J. C. Generation of a stable, posttranslationally modified microtubule array is an early event in myogenic differentiation. J. Cell Biol. 1989, 109:2275-88.
33. Gundersen, G. G. & Bulinski, J. C. Microtubule arrays in differentiated cells contain elevated levels of a post-translationally modified form of tubulin. Eur. J. Cell Biol. 1986, 42:288-94.
34. Liao, G. & Gundersen, G. G. Kinesin is a candidate for cross-bridging microtubules and intermediate filaments. Selective binding of kinesin to detyrosinated tubulin and vimentin. J. Biol. Chem. 1998, 273:9797-803.
35. Lin, S. X., Gundersen, G. G. & Maxfield, F. R. Export from pericentriolar endocytic recycling compartment to cell surface depends on stable, detyrosinated (glu) microtubules and kinesin. Mol. Biol. Cell 2002, 13:96-109.
36. Cook, T. A., Nagasaki, T. & Gundersen, G. G. Rho guanosine triphosphatase mediates the selective stabilization of microtubules induced by lysophosphatidic acid. J. Cell Biol. 1998, 141:175-85.
37. Palazzo, A. F., Cook, T. A., Alberts, A. S. & Gundersen, G. G. mDia mediates Rho-regulated formation and orientation of stable microtubules. Nat. Cell Biol. 2001, 3:723-9.
38. Wen, Y. et al. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat. Cell Biol. 2004, 6:820-30.
39. Bulinski, J. C. & Gundersen, G. G. Stabilization of post-translational modification of microtubules during cellular morphogenesis. Bioessays 1991, 13:285-93.
40. Hubbert, C. et al. HDAC6 is a microtubule-associated deacetylase. Nature 2002, 417:455-8.
41. Matsuyama, A. et al. In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. Embo J. 2002, 21:6820-31.
42. Zhang, Y. et al. HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. Embo J. 2003, 22:1168-79.
43. North, B. J., Marshall, B. L., Borra, M. T., Denu, J. M. & Verdin, E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol. Cell 2003, 11:437-44.
44. Kozminski, K. G., Diener, D. R. & Rosenbaum, J. L. High level expression of nonacetylatable alpha-tubulin in Chlamydomonas reinhardtii. Cell Motil. Cytoskeleton 1993, 25:158-70.
45. Gaertig, J. et al. Acetylation of lysine 40 in alpha-tubulin is not essential in Tetrahymena thermophila. J. Cell Biol. 1995, 129:1301-10.
46. Haggarty, S. J., Koeller, K. M., Wong, J. C., Grozinger, C. M. & Schreiber, S. L. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:4389-94.
47. Palazzo, A., Ackerman, B. & Gundersen, G. G. Cell biology: Tubulin acetylation and cell motility. Nature 2003, 421:230.
48. Hanson, C. A. & Miller, J. R. Non-traditional roles for the Adenomatous Polyposis Coli (APC) tumor suppressor protein. Gene. 2005, 361:1-12.
49. Fodde, R., Smits, R. & Clevers, H. APC, signal transduction and genetic instability in colorectal cancer. Nat. Rev. Cancer 2001, 1:55-67.
50. Morrison, E. E., Wardleworth, B. N., Askham, J. M., Markham, A. F. & Meredith, D. M. EB1, a protein which interacts with the APC tumour suppressor, is associated with the microtubule cytoskeleton throughout the cell cycle. Oncogene 1998, 17:3471-7.
51. Nakamura, M., Zhou, X. Z. & Lu, K. P. Critical role for the EB1 and APC interaction in the regulation of microtubule polymerization. Curr. Biol. 2001, 11:1062-7.
52. Lustig, B. & Behrens, J. The Wnt signaling pathway and its role in tumor development. J. Cancer Res. Clin. Oncol. 2003, 129:199-221.
53. Korinek, V. et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science 1997, 275:1784-7.
54. He, T. C. et al. Identification of c-MYC as a target of the APC pathway. Science 1998, 281:1509-12.
55. Tetsu, O. & McCormick, F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999, 398:422-6.
56. Nathke, I. S., Adams, C. L., Polakis, P., Sellin, J. H. & Nelson, W. J. The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration. J. Cell Biol. 1996, 134:165-79.
57. Zumbrunn, J., Kinoshita, K., Hyman, A. A. & Nathke, I. S. Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation. Curr. Biol. 2001, 11:44-9.
58. Su, L. K. et al. APC binds to the novel protein EB1. Cancer Res. 1995, 55:2972-7.
59. Fodde, R. et al. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat. Cell Biol. 2001, 3:433-8.
60. Kaplan, K. B. et al. A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nat. Cell Biol. 2001, 3:429-32.
61. Green, R. A. & Kaplan, K. B. Chromosome instability in colorectal tumor cells is associated with defects in microtubule plus-end attachments caused by a dominant mutation in APC. J. Cell Biol. 2003, 163:949-61.
62. Dikovskaya, D., Newton, I. P. & Nathke, I. S. The adenomatous polyposis coli protein is required for the formation of robust spindles formed in CSF Xenopus extracts. Mol. Biol. Cell 2004, 15:2978-91.
63. Brakeman, J. S., Gu, S. H., Wang, X. B., Dolin, G. & Baraban, J. M. Neuronal localization of the Adenomatous polyposis coli tumor suppressor protein. Neuroscience 1999, 91:661-72.
64. Yamanaka, H. et al. Expression of Apc2 during mouse development. Brain Res. Gene Expr. Patterns 2002, 1:107-14.
65. Dobashi, Y., Bhattacharjee, R. N., Toyoshima, K. & Akiyama, T. Upregulation of the APC gene product during neuronal differentiation of rat pheochromocytoma PC12 cells. Biochem. Biophys. Res. Commun. 1996, 224:479-83.
66. Zhou, F. Q., Zhou, J., Dedhar, S., Wu, Y. H. & Snider, W. D. NGF-induced axon growth is mediated by localized inactivation of GSK-3beta and functions of the microtubule plus end binding protein APC. Neuron 2004, 42:897-912.
67. Temburni, M. K., Rosenberg, M. M., Pathak, N., McConnell, R. & Jacob, M. H. Neuronal nicotinic synapse assembly requires the adenomatous polyposis coli tumor suppressor protein. J. Neurosci. 2004, 24:6776-84.
68. Parker, M. J., Zhao, S., Bredt, D. S., Sanes, J. R. & Feng, G. PSD93 regulates synaptic stability at neuronal cholinergic synapses. J. Neurosci. 2004, 24:378-88.
69. Nishisho, I. et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991, 253:665-9.
70. Nakagawa, H. et al. Identification of a brain-specific APC homologue, APCL, and its interaction with beta-catenin. Cancer Res. 1998, 58:5176-81.
71. van Es, J. H. et al. Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor. Curr. Biol. 1999, 9:105-8.
72. Nakagawa, H. et al. EB3, a novel member of the EB1 family preferentially expressed in the central nervous system, binds to a CNS-specific APC homologue. Oncogene 2000, 19:210-6.
73. Schwartz, K., Richards, K. & Botstein, D. BIM1 encodes a microtubule-binding protein in yeast. Mol. Biol. Cell 1997, 8:2677-91.
74. Beinhauer, J. D., Hagan, I. M., Hegemann, J. H. & Fleig, U. Mal3, the fission yeast homologue of the human APC-interacting protein EB-1 is required for microtubule integrity and the maintenance of cell form. J. Cell Biol. 1997, 139:717-28.
75. Berrueta, L., Tirnauer, J. S., Schuyler, S. C., Pellman, D. & Bierer, B. E. The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain. Curr. Biol. 1999, 9:425-8.
76. Askham, J. M., Vaughan, K. T., Goodson, H. V. & Morrison, E. E. Evidence that an interaction between EB1 and p150(Glued) is required for the formation and maintenance of a radial microtubule array anchored at the centrosome. Mol. Biol. Cell. 2002, 13:3627-45.
77. Ligon, L. A., Shelly, S. S., Tokito, M. & Holzbaur, E. L. The microtubule plus-end proteins EB1 and dynactin have differential effects on microtubule polymerization. Mol. Biol. Cell. 2003, 14:1405-17.
78. Karki, S. & Holzbaur, E. L. Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex. J. Biol. Chem. 1995, 270:28806-11.
79. Vaughan, K. T. & Vallee, R. B. Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued. J. Cell Biol. 1995, 131:1507-16.
80. Vaughan, K. T., Tynan, S. H., Faulkner, N. E., Echeverri, C. J. & Vallee, R. B. Colocalization of cytoplasmic dynein with dynactin and CLIP-170 at microtubule distal ends. J. Cell Sci. 1999, 112:1437-47.
81. Hayashi, I. & Ikura, M. Crystal structure of the amino-terminal microtubule-binding domain of end-binding protein 1 (EB1). J. Biol. Chem. 2003, 278:36430-4.
82. Bu, W. & Su, L. K. Characterization of functional domains of human EB1 family proteins. J. Biol. Chem. 2003, 278:49721-31.
83. Berrueta, L. et al. The adenomatous polyposis coli-binding protein EB1 is associated with cytoplasmic and spindle microtubules. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:10596-601.
84. Tirnauer, J. S., O'Toole, E., Berrueta, L., Bierer, B. E. & Pellman, D. Yeast Bim1p promotes the G1-specific dynamics of microtubules. J. Cell Biol. 1999, 145:993-1007.
85. Adames, N. R. & Cooper, J. A. Microtubule interactions with the cell cortex causing nuclear movements in Saccharomyces cerevisiae. J. Cell Biol. 2000, 149:863-74.
86. Korinek, W. S., Copeland, M. J., Chaudhuri, A. & Chant, J. Molecular linkage underlying microtubule orientation toward cortical sites in yeast. Science 2000, 287:2257-9.
87. Lee, L. et al. Positioning of the mitotic spindle by a cortical-microtubule capture mechanism. Science 2000, 287:2260-2.
88. Miller, R. K., Cheng, S. C. & Rose, M. D. Bim1p/Yeb1p mediates the Kar9p-dependent cortical attachment of cytoplasmic microtubules. Mol. Biol. Cell 2000, 11:2949-59.
89. Rogers, S. L., Rogers, G. C., Sharp, D. J. & Vale, R. D. Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle. J. Cell Biol. 2002, 158:873-84.
90. Lu, B., Roegiers, F., Jan, L. Y. & Jan, Y. N. Adherens junctions inhibit asymmetric division in the Drosophila epithelium. Nature 2001, 409:522-5.
91. Bu, W. & Su, L. K. Regulation of microtubule assembly by human EB1 family proteins. Oncogene 2001, 20:3185-92.
92. Juwana, J. P. et al. EB/RP gene family encodes tubulin binding proteins. Int. J. Cancer. 1999, 81:275-84.
93. Diamantopoulos, G. S. et al. Dynamic localization of CLIP-170 to microtubule plus ends is coupled to microtubule assembly. J. Cell Biol. 1999, 144:99-112.
94. Tirnauer, J. S. & Bierer, B. E. EB1 proteins regulate microtubule dynamics, cell polarity, and chromosome stability. J. Cell Biol. 2000, 149:761-6.
95. Askham, J. M., Moncur, P., Markham, A. F. & Morrison, E. E. Regulation and function of the interaction between the APC tumour suppressor protein and EB1. Oncogene 2000, 19:1950-8.
96. Munemitsu, S. et al. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res. 1994, 54:3676-81.
97. Smits, R. et al. Apc1638T: a mouse model delineating critical domains of the adenomatous polyposis coli protein involved in tumorigenesis and development. Genes Dev. 1999, 13:1309-21.
98. Trzepacz, C., Lowy, A. M., Kordich, J. J. & Groden, J. Phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) by the cyclin-dependent kinase p34. J. Biol. Chem. 1997, 272:21681-4.
99. Karki, S. & Holzbaur, E. L. Cytoplasmic dynein and dynactin in cell division and intracellular transport. Curr. Opin. Cell Biol. 1999, 11:45-53.
100. Busson, S., Dujardin, D., Moreau, A., Dompierre, J. & De, M., Jr. Dynein and dynactin are localized to astral microtubules and at cortical sites in mitotic epithelial cells. Curr. Biol. 1998, 8:541-4.
101. Skop, A. R. & White, J. G. The dynactin complex is required for cleavage plane specification in early Caenorhabditis elegans embryos. Curr. Biol. 1998, 8:1110-6.
102. Baas, P. W. & Luo, L. Signaling at the growth cone: the scientific progeny of Cajal meet in Madrid. Neuron 2001, 32:981-4.
103. Mueller, B. K. Growth cone guidance: first steps towards a deeper understanding. Annu. Rev. Neurosci. 1999, 22:351-88.
104. Dent, E. W. & Gertler, F. B. Cytoskeletal dynamics and transport in growth cone motility and axon guidance. Neuron 2003, 40:209-27.
105. Dotti, C. G., Sullivan, C. A. & Banker, G. A. The establishment of polarity by hippocampal neurons in culture. J. Neurosci. 1988, 8:1454-68.
106. Dehmelt, L. & Halpain, S. Actin and microtubules in neurite initiation: are MAPs the missing link? J. Neurobiol. 2004, 58:18-33.
107. Goldberg, D. J. & Burmeister, D. W. Stages in axon formation: observations of growth of Aplysia axons in culture using video-enhanced contrast-differential interference contrast microscopy. J. Cell Biol. 1986, 103:1921-31.
108. Stepanova, T. et al. Visualization of microtubule growth in cultured neurons via the use of EB3-GFP (end-binding protein 3-green fluorescent protein). J. Neurosci. 2003, 23:2655-64.
109. Guertin, D. A., Trautmann, S. & McCollum, D. Cytokinesis in eukaryotes. Microbiol. Mol. Biol. Rev. 2002, 66:155-78.
110. Mollinari, C. et al. PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone. J. Cell Biol. 2002, 157:1175-86.
111. Cho, H. P. et al. The dual-specificity phosphatase CDC14B bundles and stabilizes microtubules. Mol. Cell Biol. 2005, 25:4541-51.
112. Maresca, T. J., Niederstrasser, H., Weis, K. & Heald, R. Xnf7 contributes to spindle integrity through its microtubule-bundling activity. Curr. Biol. 2005, 15:1755-61.
113. Cooke, C. A., Heck, M. M. & Earnshaw, W. C. The inner centromere protein (INCENP) antigens: movement from inner centromere to midbody during mitosis. J. Cell Biol. 1987, 105:2053-67.
114. Bischoff, J. R. & Plowman, G. D. The Aurora/Ipl1p kinase family: regulators of chromosome segregation and cytokinesis. Trends Cell Biol. 1999, 9:454-9.
115. Silke, J. & Vaux, D. L. Two kinds of BIR-containing protein - inhibitors of apoptosis, or required for mitosis. J. Cell Sci. 2001, 114:1821-7.
116. Rodriguez Fernandez, J. L., Geiger, B., Salomon, D. & Ben-Ze'ev, A. Suppression of vinculin expression by antisense transfection confers changes in cell morphology, motility, and anchorage-dependent growth of 3T3 cells. J. Cell Biol. 1993, 122:1285-94.
117. Medrano, S. & Scrable, H. Maintaining appearances--the role of p53 in adult neurogenesis. Biochem. Biophys. Res. Commun. 2005, 331:828-33.
118. van Lookeren, C. M. & Gill, R. Tumor-suppressor p53 is expressed in proliferating and newly formed neurons of the embryonic and postnatal rat brain: comparison with expression of the cell cycle regulators p21Waf1/Cip1, p27Kip1, p57Kip2, p16Ink4a, cyclin G1, and the proto-oncogene Bax. J. Comp Neurol. 1998, 397:181-98.
119. Jacobs, W. B., Walsh, G. S. & Miller, F. D. Neuronal survival and p73/p63/p53: a family affair. Neuroscientist. 2004, 10:443-55.
120. Culmsee, C. & Mattson, M. P. p53 in neuronal apoptosis. Biochem. Biophys. Res. Commun. 2005, 331:761-77.
121. Reichel, M. B. et al. High frequency of persistent hyperplastic primary vitreous and cataracts in p53-deficient mice. Cell Death. Differ. 1998, 5:156-62.
122. Eizenberg, O. et al. p53 plays a regulatory role in differentiation and apoptosis of central nervous system-associated cells. Mol. Cell Biol. 1996, 16:5178-85.
123. S.Westermann, K.Weber, Post-translational modifications regulate microtubule function. Nat.Rev.Mol.Cell Biol. 2003, 4:938-47.