真核轉譯起始因子eIF4E為細胞生長之重要調控因子，在細胞核中eIF4E可調控一群具有eIF4E敏感區域（4E-SE）序列的信使RNA(mRNA)傳輸，這群信使RNA有cyclin D1、MDM2及NBS1等，而eIF4E的活性可被稱為eIF4E結合蛋白家族（4E-BPs）所調控，這個家族成員有4E-BP1、4E-BP2及4E-BP3，其中4E-BP3被報導可在細胞核及細胞質中出現，意謂4E-BP3可能參與eIF4E調控信使RNA運輸的調節。在本研究中我們改變了4E-BP3的表現（不論是過度表現或是降低表現）都發現會使cyclin D1蛋白表現量改變，而部分原因是來自於4E-BP3影響了eIF4E調控cyclin D1信使RNA在細胞質的含量，另外一方面改變4E-BP1也對於cyclin D1蛋白表現量有所影響，但主要的改變並非來自於eIF4E調控cyclin D1信使RNA在細胞質的含量。如果將野生型eIF4E或者只影響轉譯之突變型(eIF4EW73A)分別與4E-BP3在細胞中表現，會發現4E-BP3所抑制eIF4E傳輸信使RNA的功能被恢復了，但是如果是一起表現運輸缺失之突變型（eIF4EW56A）則此功能無法恢復，更進一步檢測其他也受到eIF4E所控制的信使RNA傳輸是否有受到影響（如MDM2及NBS1）也得到相同結果，證實4E-BP3影響eIF4E調控信使RNA傳送。更進一步我們發現4E-BP3與非磷酸化蛋白RPA2有交互作用且不與磷酸化蛋白RPA2作用。綜合以上我們認為4E-BP3蛋白除了抑制eIF4E所主導轉譯作用之外也是eIF4E調控信使RNA傳輸的負調節者，而4E-BP3蛋白功能則是受到RPA2蛋白磷酸化與否所控制。

Eukaryotic initiation factor 4E (eIF4E) is a critical regulator of cellular growth. Within the nucleus, eIF4E regulates the nuclear export of specific mRNAs containing 4E sensitivity elements (4E-SEs). eIF4E activity is inhibited by eIF4E-binding proteins (4E-BP1, 4E-BP2, and 4E-BP3), and 4E-BP3 is detected in both the cytoplasm and nucleus, possibly regulating eIF4E-mediated mRNA export. In this study, altered 4E-BP3 expression by knockdown or ectopic expression resulted in profoundly affected cyclin D1 protein levels, and this effect was at least in part due to changes in the cytoplasmic levels of the cyclin D1 mRNA. In contrast, although altered 4E-BP1 expression also affected cyclin D1 protein levels, its effect was not mediated through changes in cytoplasmic levels of the cyclin D1 mRNA. Co-expression of wild type or translation-deficient (W73A) eIF4E, but not by the m7G cap-binding mutant (W56A), rescued cyclin D1 protein expression in ectopic 4E-BP3 expressing cells. Furthermore, 4E-BP3 affected a subset of growth promoting mRNAs exported in an eIF4E-dependent manner, such as cyclin D1, murine double minute 2 (MDM2), and Nijmegen breakage syndrome 1 (NBS1), but not those exported in an eIF4E-independent manner, such as eIF4E and GAPDH. In addition, 4E-BP3 was found to interact with the dephosphorylated form of replication protein A2 (RPA2) but not with the phosphorylated form of RPA2. Take together, these results indicated that besides being involved in inhibition of cap-dependent translation, 4E-BP3 acts as an inhibitor of eIF4E-mediated mRNA export, and 4E-BP3 inhibition of eIF4E-mediated mRNA export is regulated by the phosphorylation state of RPA2.

1. Shimomura, O., Johnson, F.H., and Saiga, Y. 1962. Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea. J Cell Comp Physiol 59:223-239.
2. Ruggero, D., and Pandolfi, P.P. 2003. Does the ribosome translate cancer? Nat Rev Cancer 3:179-192.
3. Narla, A., and Ebert, B.L. 2010. Ribosomopathies: human disorders of ribosome dysfunction. Blood 115:3196-3205.
4. Silvera, D., Formenti, S.C., and Schneider, R.J. 2010. Translational control in cancer. Nat Rev Cancer 10:254-266.
5. Gebauer, F., and Hentze, M.W. 2004. Molecular mechanisms of translational control. Nat Rev Mol Cell Biol 5:827-835.
6. Holcik, M., and Sonenberg, N. 2005. Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 6:318-327.
7. Wilkie, G.S., Dickson, K.S., and Gray, N.K. 2003. Regulation of mRNA translation by 5'- and 3'-UTR-binding factors. Trends Biochem Sci 28:182-188.
8. Bunn, H.F., and Poyton, R.O. 1996. Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev 76:839-885.
9. Hochachka, P.W., Buck, L.T., Doll, C.J., and Land, S.C. 1996. Unifying theory of hypoxia tolerance: molecular/metabolic defense and rescue mechanisms for surviving oxygen lack. Proc Natl Acad Sci U S A 93:9493-9498.
10. Su, J.H., Chuang, Y.C., Tsai, Y.C., and Chang, M.C. 2001. Cloning and characterization of a blue fluorescent protein from Vibrio vulnificus. Biochem Biophys Res Commun 287:359-365.
11. Chang, C.C., Chuang, Y.C., and Chang, M.C. 2004. Fluorescent intensity of a novel NADPH-binding protein of Vibrio vulnificus can be improved by directed evolution. Biochem Biophys Res Commun 322:303-309.
12. Sonenberg, N., and Hinnebusch, A.G. 2009. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136:731-745.
13. Van Der Kelen, K., Beyaert, R., Inze, D., and De Veylder, L. 2009. Translational control of eukaryotic gene expression. Crit Rev Biochem Mol Biol 44:143-168.
14. Jackson, R.J., Hellen, C.U., and Pestova, T.V. 2010. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol 11:113-127.
15. Gingras, A.C., Raught, B., and Sonenberg, N. 1999. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem 68:913-963.
16. Goodfellow, I.G., and Roberts, L.O. 2008. Eukaryotic initiation factor 4E. Int J Biochem Cell Biol 40:2675-2680.
17. Sonenberg, N., and Hinnebusch, A.G. 2007. New modes of translational control in development, behavior, and disease. Mol Cell 28:721-729.
18. Keene, J.D. 2007. RNA regulons: coordination of post-transcriptional events. Nat Rev Genet 8:533-543.
19. Culjkovic, B., Tan, K., Orolicki, S., Amri, A., Meloche, S., and Borden, K.L. 2008. The eIF4E RNA regulon promotes the Akt signaling pathway. J Cell Biol 181:51-63.
20. Culjkovic, B., Topisirovic, I., and Borden, K.L. 2007. Controlling gene expression through RNA regulons: the role of the eukaryotic translation initiation factor eIF4E. Cell Cycle 6:65-69.
21. Culjkovic, B., Topisirovic, I., Skrabanek, L., Ruiz-Gutierrez, M., and Borden, K.L. 2005. eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3'UTR. J Cell Biol 169:245-256.
22. Culjkovic, B., Topisirovic, I., Skrabanek, L., Ruiz-Gutierrez, M., and Borden, K.L. 2006. eIF4E is a central node of an RNA regulon that governs cellular proliferation. J Cell Biol 175:415-426.
23. Stebbins-Boaz, B., Cao, Q., de Moor, C.H., Mendez, R., and Richter, J.D. 1999. Maskin is a CPEB-associated factor that transiently interacts with elF-4E. Mol Cell 4:1017-1027.
24. Niessing, D., Blanke, S., and Jackle, H. 2002. Bicoid associates with the 5'-cap-bound complex of caudal mRNA and represses translation. Genes Dev 16:2576-2582.
25. Wilhelm, J.E., Hilton, M., Amos, Q., and Henzel, W.J. 2003. Cup is an eIF4E binding protein required for both the translational repression of oskar and the recruitment of Barentsz. J Cell Biol 163:1197-1204.
26. Shih, J.W., Tsai, T.Y., Chao, C.H., and Wu Lee, Y.H. 2008. Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein. Oncogene 27:700-714.
27. Topisirovic, I., Culjkovic, B., Cohen, N., Perez, J.M., Skrabanek, L., and Borden, K.L. 2003. The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth. The EMBO journal 22:689-703.
28. Richter, J.D., and Sonenberg, N. 2005. Regulation of cap-dependent translation by eIF4E inhibitory proteins. Nature 433:477-480.
29. Gingras, A.C., Raught, B., Gygi, S.P., Niedzwiecka, A., Miron, M., Burley, S.K., Polakiewicz, R.D., Wyslouch-Cieszynska, A., Aebersold, R., and Sonenberg, N. 2001. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev 15:2852-2864.
30. Poulin, F., Gingras, A.C., Olsen, H., Chevalier, S., and Sonenberg, N. 1998. 4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family. J Biol Chem 273:14002-14007.
31. Kleijn, M., Scheper, G.C., Wilson, M.L., Tee, A.R., and Proud, C.G. 2002. Localisation and regulation of the eIF4E-binding protein 4E-BP3. FEBS Lett 532:319-323.
32. Wold, M.S. 1997. Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu Rev Biochem 66:61-92.
33. Fanning, E., Klimovich, V., and Nager, A.R. 2006. A dynamic model for replication protein A (RPA) function in DNA processing pathways. Nucleic Acids Res 34:4126-4137.
34. Zhang, X., Shu, L., Hosoi, H., Murti, K.G., and Houghton, P.J. 2002. Predominant nuclear localization of mammalian target of rapamycin in normal and malignant cells in culture. J Biol Chem 277:28127-28134.
35. Rong, L., Livingstone, M., Sukarieh, R., Petroulakis, E., Gingras, A.C., Crosby, K., Smith, B., Polakiewicz, R.D., Pelletier, J., Ferraiuolo, M.A., et al. 2008. Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs. Rna 14:1318-1327.
36. Rousseau, D., Kaspar, R., Rosenwald, I., Gehrke, L., and Sonenberg, N. 1996. Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E. Proc Natl Acad Sci U S A 93:1065-1070.
37. Cohen, N., Sharma, M., Kentsis, A., Perez, J.M., Strudwick, S., and Borden, K.L. 2001. PML RING suppresses oncogenic transformation by reducing the affinity of eIF4E for mRNA. EMBO J 20:4547-4559.
38. Poulin, F., Brueschke, A., and Sonenberg, N. 2003. Gene fusion and overlapping reading frames in the mammalian genes for 4E-BP3 and MASK. J Biol Chem 278:52290-52297.
39. Sukarieh, R., Sonenberg, N., and Pelletier, J. 2009. The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response. Am J Physiol Cell Physiol 296:C1207-1217.
40. Averous, J., Fonseca, B.D., and Proud, C.G. 2008. Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1. Oncogene 27:1106-1113.
41. Binz, S.K., Sheehan, A.M., and Wold, M.S. 2004. Replication protein A phosphorylation and the cellular response to DNA damage. DNA Repair (Amst) 3:1015-1024.
42. Zou, Y., Liu, Y., Wu, X., and Shell, S.M. 2006. Functions of human replication protein A (RPA): from DNA replication to DNA damage and stress responses. J Cell Physiol 208:267-273.
43. Prasher, D.C., Eckenrode, V.K., Ward, W.W., Prendergast, F.G., and Cormier, M.J. 1992. Primary structure of the Aequorea victoria green-fluorescent protein. Gene
44. Chalfie, M., Tu, Y., Euskirchen, G., Ward, W.W., and Prasher, D.C. 1994. Green fluorescent protein as a marker for gene expression. Science 263:802-805.
45. Tsien, R.Y. 1998. The green fluorescent protein. Annu Rev Biochem 67:509-544.
46. Shaner, N.C., Steinbach, P.A., and Tsien, R.Y. 2005. A guide to choosing fluorescent proteins. Nat Methods 2:905-909.
47. Stepanenko, O.V., Verkhusha, V.V., Kuznetsova, I.M., Uversky, V.N., and Turoverov, K.K. 2008. Fluorescent proteins as biomarkers and biosensors: throwing color lights on molecular and cellular processes. Curr Protein Pept Sci 9:338-369.
48. Pakhomov, A.A., and Martynov, V.I. 2008. GFP family: structural insights into spectral tuning. Chem Biol 15:755-764.
49. Verkhusha, V.V., Kuznetsova, I.M., Stepanenko, O.V., Zaraisky, A.G., Shavlovsky, M.M., Turoverov, K.K., and Uversky, V.N. 2003. High stability of Discosoma DsRed as compared to Aequorea EGFP. Biochemistry 42:7879-7884.
50. Lemay, N.P., Morgan, A.L., Archer, E.J., Dickson, L.A., Megley, C.M., and Zimmer, M. 2008. The Role of the Tight-Turn, Broken Hydrogen Bonding, Glu222 and Arg96 in the Post-translational Green Fluorescent Protein Chromophore Formation. Chem Phys 348:152-160.
51. Ormo, M., Cubitt, A.B., Kallio, K., Gross, L.A., Tsien, R.Y., and Remington, S.J. 1996. Crystal structure of the Aequorea victoria green fluorescent protein. Science 273:1392-1395.
52. Zimmermann, T., Rietdorf, J., Girod, A., Georget, V., and Pepperkok, R. 2002. Spectral imaging and linear un-mixing enables improved FRET efficiency with a novel GFP2-YFP FRET pair. FEBS Lett 531:245-249.
53. Patterson, G.H., and Lippincott-Schwartz, J. 2002. A photoactivatable GFP for selective photolabeling of proteins and cells. Science 297:1873-1877.
54. Bulina, M.E., Chudakov, D.M., Mudrik, N.N., and Lukyanov, K.A. 2002. Interconversion of Anthozoa GFP-like fluorescent and non-fluorescent proteins by mutagenesis. BMC Biochem 3:7.
55. Matz, M.V., Fradkov, A.F., Labas, Y.A., Savitsky, A.P., Zaraisky, A.G., Markelov, M.L., and Lukyanov, S.A. 1999. Fluorescent proteins from nonbioluminescent Anthozoa species. Nat Biotechnol 17:969-973.
56. Strack, R.L., Strongin, D.E., Mets, L., Glick, B.S., and Keenan, R.J. 2010. Chromophore formation in DsRed occurs by a branched pathway. J Am Chem Soc 132:8496-8505.
57. Subach, O.M., Malashkevich, V.N., Zencheck, W.D., Morozova, K.S., Piatkevich, K.D., Almo, S.C., and Verkhusha, V.V. 2010. Structural characterization of acylimine-containing blue and red chromophores in mTagBFP and TagRFP fluorescent proteins. Chem Biol 17:333-341.
58. Tsien, R.Y. 2003. Imagining imaging's future. Nat Rev Mol Cell Biol Suppl:SS16-21.
59. Giepmans, B.N., Adams, S.R., Ellisman, M.H., and Tsien, R.Y. 2006. The fluorescent toolbox for assessing protein location and function. Science 312:217-224.
60. Heim, R., and Tsien, R.Y. 1996. Engineering green fluorescent protein for improved brightness, longer wavelengths and fluorescence resonance energy transfer. Curr Biol 6:178-182.
61. Yang, T.T., Sinai, P., Green, G., Kitts, P.A., Chen, Y.T., Lybarger, L., Chervenak, R., Patterson, G.H., Piston, D.W., and Kain, S.R. 1998. Improved fluorescence and dual color detection with enhanced blue and green variants of the green fluorescent protein. J Biol Chem 273:8212-8216.
62. Kremers, G.J., Goedhart, J., van den Heuvel, D.J., Gerritsen, H.C., and Gadella, T.W., Jr. 2007. Improved green and blue fluorescent proteins for expression in bacteria and mammalian cells. Biochemistry 46:3775-3783.
63. Ai, H.W., Shaner, N.C., Cheng, Z., Tsien, R.Y., and Campbell, R.E. 2007. Exploration of new chromophore structures leads to the identification of improved blue fluorescent proteins. Biochemistry 46:5904-5910.
64. Mena, M.A., Treynor, T.P., Mayo, S.L., and Daugherty, P.S. 2006. Blue fluorescent proteins with enhanced brightness and photostability from a structurally targeted library. Nat Biotechnol 24:1569-1571.
65. Tomosugi, W., Matsuda, T., Tani, T., Nemoto, T., Kotera, I., Saito, K., Horikawa, K., and Nagai, T. 2009. An ultramarine fluorescent protein with increased photostability and pH insensitivity. Nat Methods 6:351-353.
66. van der Horst, M.A., and Hellingwerf, K.J. 2004. Photoreceptor proteins, "star actors of modern times": a review of the functional dynamics in the structure of representative members of six different photoreceptor families. Acc Chem Res 37:13-20.
67. Moglich, A., Yang, X., Ayers, R.A., and Moffat, K. 2010. Structure and function of plant photoreceptors. Annu Rev Plant Biol 61:21-47.
68. Salomon, M., Eisenreich, W., Durr, H., Schleicher, E., Knieb, E., Massey, V., Rudiger, W., Muller, F., Bacher, A., and Richter, G. 2001. An optomechanical transducer in the blue light receptor phototropin from Avena sativa. Proc Natl Acad Sci U S A 98:12357-12361.
69. Christie, J.M., Corchnoy, S.B., Swartz, T.E., Hokenson, M., Han, I.S., Briggs, W.R., and Bogomolni, R.A. 2007. Steric interactions stabilize the signaling state of the LOV2 domain of phototropin 1. Biochemistry 46:9310-9319.
70. Yang, X., Kuk, J., and Moffat, K. 2008. Crystal structure of Pseudomonas aeruginosa bacteriophytochrome: photoconversion and signal transduction. Proc Natl Acad Sci U S A 105:14715-14720.
71. Drepper, T., Eggert, T., Circolone, F., Heck, A., Krauss, U., Guterl, J.K., Wendorff, M., Losi, A., Gartner, W., and Jaeger, K.E. 2007. Reporter proteins for in vivo fluorescence without oxygen. Nat Biotechnol 25:443-445.
72. Drepper, T., Huber, R., Heck, A., Circolone, F., Hillmer, A.K., Buchs, J., and Jaeger, K.E. 2010. Flavin mononucleotide-based fluorescent reporter proteins outperform green fluorescent protein-like proteins as quantitative in vivo real-time reporters. Appl Environ Microbiol 76:5990-5994.
73. Krol, J.E., Rogers, L.M., Krone, S.M., and Top, E.M. 2010. Dual reporter system for in situ detection of plasmid transfer under aerobic and anaerobic conditions. Appl Environ Microbiol 76:4553-4556.
74. Krauss, U., Minh, B.Q., Losi, A., Gartner, W., Eggert, T., von Haeseler, A., and Jaeger, K.E. 2009. Distribution and phylogeny of light-oxygen-voltage-blue-light-signaling proteins in the three kingdoms of life. J Bacteriol 191:7234-7242.
75. Tielker, D., Eichhof, I., Jaeger, K.E., and Ernst, J.F. 2009. Flavin mononucleotide-based fluorescent protein as an oxygen-independent reporter in Candida albicans and Saccharomyces cerevisiae. Eukaryot Cell 8:913-915.
76. Numann, R., and Negulescu, P.A. 2001. High-throughput screening strategies for cardiac ion channels. Trends Cardiovasc Med 11:54-59.
77. Ottolia, M., John, S., Xie, Y., Ren, X., and Philipson, K.D. 2007. Shedding light on the Na+/Ca2+ exchanger. Ann N Y Acad Sci 1099:78-85.
78. Wang, Q., Chen, B., Liu, P., Zheng, M., Wang, Y., Cui, S., Sun, D., Fang, X., Liu, C.M., Lucas, W.J., et al. 2009. Calmodulin binds to extracellular sites on the plasma membrane of plant cells and elicits a rise in intracellular calcium concentration. J Biol Chem 284:12000-12007.
79. Hayes, N., Howard-Cofield, E., and Gullick, W. 2004. Green fluorescent protein as a tool to study epidermal growth factor receptor function. Cancer Lett 206:129-135.
80. Wu, Y., Kim, S.G., Xing, D., Liu, L., Park, J.C., Chen, T., and Chen, W.R. 2007. Fluorescence resonance energy transfer analysis of bid activation in living cells during ultraviolet-induced apoptosis. Acta Biochim Biophys Sin (Shanghai) 39:37-45.
81. Iancu, R.V., Ramamurthy, G., and Harvey, R.D. 2008. Spatial and temporal aspects of cAMP signalling in cardiac myocytes. Clin Exp Pharmacol Physiol 35:1343-1348.
82. Liang, G.X., Pan, H.C., Li, Y., Jiang, L.P., Zhang, J.R., and Zhu, J.J. 2009. Near infrared sensing based on fluorescence resonance energy transfer between Mn:CdTe quantum dots and Au nanorods. Biosens Bioelectron 24:3693-3697.
83. Wouters, F.S., and Bastiaens, P.I. 1999. Fluorescence lifetime imaging of receptor tyrosine kinase activity in cells. Curr Biol 9:1127-1130.
84. Kraynov, V.S., Chamberlain, C., Bokoch, G.M., Schwartz, M.A., Slabaugh, S., and Hahn, K.M. 2000. Localized Rac activation dynamics visualized in living cells. Science 290:333-337.
85. Mochizuki, N., Yamashita, S., Kurokawa, K., Ohba, Y., Nagai, T., Miyawaki, A., and Matsuda, M. 2001. Spatio-temporal images of growth-factor-induced activation of Ras and Rap1. Nature 411:1065-1068.
86. DiPilato, L.M., and Zhang, J. 2009. The role of membrane microdomains in shaping beta2-adrenergic receptor-mediated cAMP dynamics. Mol Biosyst 5:832-837.
87. Oppermann, U., Filling, C., Hult, M., Shafqat, N., Wu, X., Lindh, M., Shafqat, J., Nordling, E., Kallberg, Y., Persson, B., et al. 2003. Short-chain dehydrogenases/reductases (SDR): the 2002 update. Chem Biol Interact 143-144:247-253.
88. Chang, C.C., Chuang, Y.C., Chen, Y.C., and Chang, M.C. 2004. Bright fluorescence of a novel protein from Vibrio vulnificus depends on NADPH and the expression of this protein is regulated by a LysR-type regulatory gene. Biochem Biophys Res Commun 319:207-213.
89. Chang, T.W., Chen, C.C., Chen, K.Y., Su, J.H., Chang, J.H., and Chang, M.C. 2008. Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells. Oncogene 27:332-338.
90. Dewhirst, M.W., Cao, Y., and Moeller, B. 2008. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nat Rev Cancer 8:425-437.
91. Wilson, W.R., and Hay, M.P. 2011. Targeting hypoxia in cancer therapy. Nat Rev Cancer 11:393-410.
92. Wool, I.G., Chan, Y.L., Gluck, A., and Suzuki, K. 1991. The primary structure of rat ribosomal proteins P0, P1, and P2 and a proposal for a uniform nomenclature for mammalian and yeast ribosomal proteins. Biochimie 73:861-870.
93. Remacha, M., Jimenez-Diaz, A., Santos, C., Briones, E., Zambrano, R., Rodriguez Gabriel, M.A., Guarinos, E., and Ballesta, J.P. 1995. Proteins P1, P2, and P0, components of the eukaryotic ribosome stalk. New structural and functional aspects. Biochem Cell Biol 73:959-968.
94. Grabowski, D.T., Pieper, R.O., Futscher, B.W., Deutsch, W.A., Erickson, L.C., and Kelley, M.R. 1992. Expression of ribosomal phosphoprotein PO is induced by antitumor agents and increased in Mer- human tumor cell lines. Carcinogenesis 13:259-263.
95. Barnard, G.F., Staniunas, R.J., Bao, S., Mafune, K., Steele, G.D., Jr., Gollan, J.L., and Chen, L.B. 1992. Increased expression of human ribosomal phosphoprotein P0 messenger RNA in hepatocellular carcinoma and colon carcinoma. Cancer Res 52:3067-3072.
96. Kondoh, N., Wakatsuki, T., Ryo, A., Hada, A., Aihara, T., Horiuchi, S., Goseki, N., Matsubara, O., Takenaka, K., Shichita, M., et al. 1999. Identification and characterization of genes associated with human hepatocellular carcinogenesis. Cancer Res 59:4990-4996.
97. Xia, C., Bao, Z., Tabassam, F., Ma, W., Qiu, M., Hua, S., and Liu, M. 2000. GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity. J Biol Chem 275:20942-20948.
98. Terai, S., Aoki, H., Ashida, K., and Thorgeirsson, S.S. 2000. Human homologue of maid: A dominant inhibitory helix-loop-helix protein associated with liver-specific gene expression. Hepatology 32:357-366.
99. Yao, Y., Doki, Y., Jiang, W., Imoto, M., Venkatraj, V.S., Warburton, D., Santella, R.M., Lu, B., Yan, L., Sun, X.H., et al. 2000. Cloning and characterization of DIP1, a novel protein that is related to the Id family of proteins. Exp Cell Res 257:22-32.
100. Tchorzewski, M., Krokowski, D., Rzeski, W., Issinger, O.G., and Grankowski, N. 2003. The subcellular distribution of the human ribosomal "stalk" components: P1, P2 and P0 proteins. Int J Biochem Cell Biol 35:203-211.
101. Ma, W., Xia, X., Stafford, L.J., Yu, C., Wang, F., LeSage, G., and Liu, M. 2006. Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis. Oncogene 25:4207-4216.
102. Kitagawa, M., Higashi, H., Jung, H.K., Suzuki-Takahashi, I., Ikeda, M., Tamai, K., Kato, J., Segawa, K., Yoshida, E., Nishimura, S., et al. 1996. The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J 15:7060-7069.
103. Takami, T., Terai, S., Yokoyama, Y., Tanimoto, H., Tajima, K., Uchida, K., Yamasaki, T., Sakaida, I., Nishina, H., Thorgeirsson, S.S., et al. 2005. Human homologue of maid is a useful marker protein in hepatocarcinogenesis. Gastroenterology 128:1369-1380.
104. Sonnenberg-Riethmacher, E., Wustefeld, T., Miehe, M., Trautwein, C., and Riethmacher, D. 2007. Maid (GCIP) is involved in cell cycle control of hepatocytes. Hepatology 45:404-411.
105. Ma, W., Stafford, L.J., Li, D., Luo, J., Li, X., Ning, G., and Liu, M. 2007. GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis. J Cell Biochem 100:1376-1386.
106. Uchiumi, T., and Kominami, R. 1997. Binding of mammalian ribosomal protein complex P0.P1.P2 and protein L12 to the GTPase-associated domain of 28 S ribosomal RNA and effect on the accessibility to anti-28 S RNA autoantibody. J Biol Chem 272:3302-3308.
107. Shimizu, T., Nakagaki, M., Nishi, Y., Kobayashi, Y., Hachimori, A., and Uchiumi, T. 2002. Interaction among silkworm ribosomal proteins P1, P2 and P0 required for functional protein binding to the GTPase-associated domain of 28S rRNA. Nucleic Acids Res 30:2620-2627.
108. Wu, S., and Storey, K.B. 2005. Up-regulation of acidic ribosomal phosphoprotein P0 in response to freezing or anoxia in the freeze tolerant wood frog, Rana sylvatica. Cryobiology 50:71-82.
109. Chang, M.S., Chang, C.L., Huang, C.J., and Yang, Y.C. 2000. p29, a novel GCIP-interacting protein, localizes in the nucleus. Biochem Biophys Res Commun 279:732-737.
110. Diehl, J.A. 2002. Cycling to cancer with cyclin D1. Cancer Biol Ther 1:226-231.
111. Hosokawa, Y., and Arnold, A. 1996. Cyclin D1/PRAD1 as a central target in oncogenesis. J Lab Clin Med 127:246-252.