過去已知在壓力之下，細胞中蛋白質的生合成會被抑制，然而部分的基因會透過其他的轉譯起始機制(Translation initiation)，例如：核醣體進入位點(internal ribosome entry site; IRES)，來維持基因的表達並促進蛋白質生合成以利細胞的存活。傳統的轉譯起始機制 (cap-dependent translation initiation)已經被廣泛研究，然而細胞內受到IRES調控的機制目前仍然屬於未知，並尚未被廣泛的研究。另一方面，在病毒中受IRES調控的轉譯起始機制已經被研究超過30年，而且根據它們所需要的轉譯起始因子(eukaryotic initiation factor；eIF)、RNA結構以及核醣體進入位點與轉譯起始點(translation start site)的距離主要被歸類成4大類。我們實驗室過去的研究中發現，在缺氧(Hypoxia)的狀態下，纖維母細胞生長因子細胞9 (Fibroblast growth factor 9；FGF9)的蛋白質生的量會上升，然而RNA的量不但沒有增加反而些微下降，顯示出在缺氧的狀態下FGF9轉譯效率提升。因此更進一步探討我們發現FGF9透過訊息RNA (mRNA)5端為轉譯區(5’UTR)中的IRES序列去促進缺氧誘導，受IRES調控的轉譯機制。然而，所需要的因子，以及參與在這個調控的分子機轉目前仍然是未知的。根據我們對FGF9 5’UTR所做的結構分析，我們發現與第二類病毒IRES有些類似都具有一個Y型的結構，以及IRES到轉譯起始點的距離都為40nt，因此我們假設受IRES調控的FGF9轉譯起始機轉是相類似的，需要大多數的轉譯起始因子除了轉譯起始因子4E, 5端帽結合蛋白。因此在本次的研究中我們希望找出在缺氧環境下IRES調控的FGF9轉譯起始因子。我們對HEK293細胞進行常氧(Normoxia；21% O2)與缺氧(Hypoxia；1% O2)的處理，並收下全細胞蛋白質或核質分離後的細胞質蛋白，並利用人工合成具有biotin修飾的FGF9 5’UTR以及IRES探針去抓下與RNA結合的這些蛋白，接著利用質譜儀分析去鑑定蛋白質的身分。後續我們針對在不同組別(Normoxia vs Hypoxia, FL vs IRES)與不同批次(whole cell lysate, cytosolic fraction)的的實驗中鑑定到因子進行生物資訊的分析，以及蛋白功能得註解。我們發現大多數的因子參與在轉譯起始的調控上，有部分因子是已知起始因子的同源蛋白。我們預期本次的研究可以加深我們對於在缺氧下，受IRES調控的轉譯活化有更深的認識。

Under stress conditions, cells can bypass the inhibition of cap-dependent mechanism to sustain the protein expression by internal ribosome entry site (IRES)-mediated translation. While cap-dependent translation initiation has been well characterized, the underlying mechanism of cellular IRES-mediated translation is still unclear. On the other hand, IRES-mediated translation is common in virus. Four types of viral IRESs have been classified based on their requirements of co-factor (eIFs), RNA structures and distances between IRES and initiation codon. Our previous study found that the protein synthesis of Fibroblast growth factor 9 (FGF9) is upregulated under hypoxia through IRES-mediated translational activation. However, the molecular mechanism and factors involve in hypoxia-induced IRES-mediated FGF9 translational initiation is still unknown. As the structure of FGF9 5’UTR is similar to type II viral IRES, we hypothesize the initiation of FGF9 IRES-mediated translation under hypoxia may involve most of the eukaryotic initiation factors (eIFs) except eIF4E. In this study, we aim to identify the members of translation initiation complex that interact with the 5’UTR of FGF9 transcript to trigger FGF9 protein synthesis in low oxygen condition. RNA pull-down assays were performed by using biotin-labelled full-length 5’UTR and IRES of FGF9 mRNA to incubate with the lysates from normoxic or hypoxic HEK293 cells and captured by streptavidin beads. Followed by LC/MS/MS and Mascot MS/MS Ions Search analysis to identify factors that interact with FGF9 5’UTR. Lists of factors had been identified from different groups (Normoxia vs Hypoxia, FL vs IRES) and different batches (Whole cell lysate and cytosolic fraction). Further annotation of identified proteins showed an enrichment of proteins involved in the translation and many of them are homologs of known initiation factors. We expect results from this study improve our understanding on the mechanism of hypoxia-induced IRES-mediated translational activation.

References
Abdelmohsen, Kotb. 2012. 'Modulation of Gene Expression by RNA Binding Proteins: mRNA Stability and Translation.' in, Binding Protein.
Asnani, M., P. Kumar, and C. U. Hellen. 2015. 'Widespread distribution and structural diversity of Type IV IRESs in members of Picornaviridae', Virology, 478: 61-74.
Barak, H., S. H. Huh, S. Chen, C. Jeanpierre, J. Martinovic, M. Parisot, C. Bole-Feysot, P. Nitschke, R. Salomon, C. Antignac, D. M. Ornitz, and R. Kopan. 2012. 'FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man', Developmental Cell, 22: 1191-207.
Bhattacharya, R., S. Ray Chaudhuri, and S. S. Roy. 2018. 'FGF9-induced ovarian cancer cell invasion involves VEGF-A/VEGFR2 augmentation by virtue of ETS1 upregulation and metabolic reprogramming', Journal of Cellular Biochemistry, 119: 8174-89.
Chapat, C., S. M. Jafarnejad, E. Matta-Camacho, G. G. Hesketh, I. A. Gelbart, J. Attig, C. G. Gkogkas, T. Alain, N. Stern-Ginossar, M. R. Fabian, A. C. Gingras, T. F. Duchaine, and N. Sonenberg. 2017. 'Cap-binding protein 4EHP effects translation silencing by microRNAs', Proceedings of the National Academy of Sciences of the United States of America, 114: 5425-30.
Chen, J. T., C. C. Liu, J. S. Yu, H. H. Li, and M. C. Lai. 2018. 'Integrated omics profiling identifies hypoxia-regulated genes in HCT116 colon cancer cells', Journal of Proteomics, 188: 139-51.
Chen, T. M., C. H. Hsu, S. J. Tsai, and H. S. Sun. 2010. 'AUF1 p42 isoform selectively controls both steady-state and PGE2-induced FGF9 mRNA decay', Nucleic Acids Research, 38: 8061-71.
Chen, T. M., P. L. Kuo, C. H. Hsu, S. J. Tsai, M. J. Chen, C. W. Lin, and H. S. Sun. 2007. 'Microsatellite in the 3' untranslated region of human fibroblast growth factor 9 (FGF9) gene exhibits pleiotropic effect on modulating FGF9 protein expression', Human Mutation, 28: 98.
Chen, T. M., M. C. Lai, Y. H. Li, Y. L. Chan, C. H. Wu, Y. M. Wang, C. W. Chien, S. Y. Huang, H. S. Sun, and S. J. Tsai. 2019. 'hnRNPM induces translation switch under hypoxia to promote colon cancer development', EBioMedicine, 41: 299-309.
Chen, T. M., Y. H. Shih, J. T. Tseng, M. C. Lai, C. H. Wu, Y. H. Li, S. J. Tsai, and H. S. Sun. 2014. 'Overexpression of FGF9 in colon cancer cells is mediated by hypoxia-induced translational activation', Nucleic Acids Research, 42: 2932-44.
Choe, J., S. Lin, W. Zhang, Q. Liu, L. Wang, J. Ramirez-Moya, P. Du, W. Kim, S. Tang, P. Sliz, P. Santisteban, R. E. George, W. G. Richards, K. K. Wong, N. Locker, F. J. Slack, and R. I. Gregory. 2018. 'mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis', Nature, 561: 556-60.
Chuang, P. C., H. S. Sun, T. M. Chen, and S. J. Tsai. 2006. 'Prostaglandin E2 induces fibroblast growth factor 9 via EP3-dependent protein kinase Cdelta and Elk-1 signaling', Molecular and Cellular Biology, 26: 8281-92.
Colvin, J. S., B. Feldman, J. H. Nadeau, M. Goldfarb, and D. M. Ornitz. 1999. 'Genomic organization and embryonic expression of the mouse fibroblast growth factor 9 gene', Developmental Dynamics, 216: 72-88.
Colvin, J. S., R. P. Green, J. Schmahl, B. Capel, and D. M. Ornitz. 2001. 'Male-to-female sex reversal in mice lacking fibroblast growth factor 9', Cell, 104: 875-89.
Colvin, J. S., A. C. White, S. J. Pratt, and D. M. Ornitz. 2001. 'Lung hypoplasia and neonatal death in Fgf9-null mice identify this gene as an essential regulator of lung mesenchyme', Development, 128: 2095-106.
Connolly, E., S. Braunstein, S. Formenti, and R. J. Schneider. 2006. 'Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells', Molecular and Cellular Biology, 26: 3955-65.
Costa-Mattioli, Mauro, Yuri Svitkin, and Nahum Sonenberg. 2004. 'La Autoantigen Is Necessary for Optimal Function of the Poliovirus and Hepatitis C Virus Internal Ribosome Entry Site In Vivo and In Vitro', Molecular and Cellular Biology, 24: 6861-70.
Etchison, D., S. C. Milburn, I. Edery, N. Sonenberg, and J. W. Hershey. 1982. 'Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000-dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex', Journal of Biological Chemistry, 257: 14806-10.
Evans, Joanne R., Sally A. Mitchell, Keith A. Spriggs, Jerzy Ostrowski, Karol Bomsztyk, Dirk Ostarek, and Anne E. Willis. 2003. 'Members of the poly (rC) binding protein family stimulate the activity of the c-myc internal ribosome entry segment in vitro and in vivo', Oncogene, 22: 8012-20.
Fraser, C. S., J. W. Hershey, and J. A. Doudna. 2009. 'The pathway of hepatitis C virus mRNA recruitment to the human ribosome', Nature Structural & Molecular Biology, 16: 397-404.
Fuchs, G., A. N. Petrov, C. D. Marceau, L. M. Popov, J. Chen, S. E. O'Leary, R. Wang, J. E. Carette, P. Sarnow, and J. D. Puglisi. 2015. 'Kinetic pathway of 40S ribosomal subunit recruitment to hepatitis C virus internal ribosome entry site', Proceedings of the National Academy of Sciences of the United States of America, 112: 319-25.
Gao, X., J. Wan, B. Liu, M. Ma, B. Shen, and S. B. Qian. 2015. 'Quantitative profiling of initiating ribosomes in vivo', Nature Methods, 12: 147-53.
Gau, B. H., T. M. Chen, Y. H. Shih, and H. S. Sun. 2011. 'FUBP3 interacts with FGF9 3' microsatellite and positively regulates FGF9 translation', Nucleic Acids Research, 39: 3582-93.
Gingras, A. C., Y. Svitkin, G. J. Belsham, A. Pause, and N. Sonenberg. 1996. 'Activation of the translational suppressor 4E-BP1 following infection with encephalomyocarditis virus and poliovirus', Proceedings of the National Academy of Sciences of the United States of America, 93: 5578-83.
Godet, A. C., F. David, F. Hantelys, F. Tatin, E. Lacazette, B. Garmy-Susini, and A. C. Prats. 2019. 'IRES Trans-Acting Factors, Key Actors of the Stress Response', International Journal of Molecular Sciences, 20: 924.
Gradi, A., Y. V. Svitkin, H. Imataka, and N. Sonenberg. 1998. 'Proteolysis of human eukaryotic translation initiation factor eIF4GII, but not eIF4GI, coincides with the shutoff of host protein synthesis after poliovirus infection', Proceedings of the National Academy of Sciences of the United States of America, 95: 11089-94.
Hertz, Marla I., Dori M. Landry, Anne E. Willis, Guangxiang Luo, and Sunnie R. Thompson. 2013. 'Ribosomal Protein S25 Dependency Reveals a Common Mechanism for Diverse Internal Ribosome Entry Sites and Ribosome Shunting', Molecular and Cellular Biology, 33: 1016-26.
Ho, J. J. David, Miling Wang, Timothy E Audas, Deukwoo Kwon, Steven K Carlsson, Sara Timpano, Sonia L Evagelou, Shaun Brothers, Mark L Gonzalgo, Jonathan R Krieger, Steven Chen, James Uniacke, and Stephen Lee. 2016. 'Systemic Reprogramming of Translation Efficiencies on Oxygen Stimulus', Cell Reports, 14: 1293-300.
Hochachka, P. W., L. T. Buck, C. J. Doll, and S. C. Land. 1996. 'Unifying theory of hypoxia tolerance: molecular/metabolic defense and rescue mechanisms for surviving oxygen lack', Proceedings of the National Academy of Sciences of the United States of America, 93: 9493-8.
Holcik, M., and N. Sonenberg. 2005. 'Translational control in stress and apoptosis', Nature Reviews: Molecular Cell Biology, 6: 318-27.
Holcik, Martin, and Robert G. Korneluk. 2000. 'Functional Characterization of the X-Linked Inhibitor of Apoptosis (XIAP) Internal Ribosome Entry Site Element: Role of La Autoantigen in XIAP Translation', Molecular and Cellular Biology, 20: 4648-57.
Ingolia, N. T., L. F. Lareau, and J. S. Weissman. 2011. 'Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes', Cell, 147: 789-802.
Itoh, N., Y. Nakayama, and M. Konishi. 2016. 'Roles of FGFs As Paracrine or Endocrine Signals in Liver Development, Health, and Disease', Front Cell Dev Biol, 4: 30.
Jackson, R. J., C. U. Hellen, and T. V. Pestova. 2010. 'The mechanism of eukaryotic translation initiation and principles of its regulation', Nature Reviews: Molecular Cell Biology, 11: 113-27.
Jang, S. K., H. G. Krausslich, M. J. Nicklin, G. M. Duke, A. C. Palmenberg, and E. Wimmer. 1988. 'A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation', Journal of Virology, 62: 2636-43.
Jensen, K. B., and R. B. Darnell. 2008. 'CLIP: crosslinking and immunoprecipitation of in vivo RNA targets of RNA-binding proteins', Methods in Molecular Biology, 488: 85-98.
Kerr, C. H., and E. Jan. 2016. 'Commandeering the Ribosome: Lessons Learned from Dicistroviruses about Translation', Journal of Virology, 90: 5538-40.
Kieft, J. S. 2008. 'Viral IRES RNA structures and ribosome interactions', Trends in Biochemical Sciences, 33: 274-83.
Kim, Yoon Ki, Sung Hoon Back, Jungmin Rho, Song Hee Lee, and Sung Key Jang. 2001. 'La autoantigen enhances translation of BiP mRNA', Nucleic Acids Research, 29: 5009-16.
Koumenis, C., C. Naczki, M. Koritzinsky, S. Rastani, A. Diehl, N. Sonenberg, A. Koromilas, and B. G. Wouters. 2002. 'Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha', Molecular and Cellular Biology, 22: 7405-16.
Kuyumcu-Martinez, N. M., M. Joachims, and R. E. Lloyd. 2002. 'Efficient cleavage of ribosome-associated poly(A)-binding protein by enterovirus 3C protease', Journal of Virology, 76: 2062-74.
Lacerda, R., J. Menezes, and L. Romao. 2017. 'More than just scanning: the importance of cap-independent mRNA translation initiation for cellular stress response and cancer', Cellular and Molecular Life Sciences, 74: 1659-80.
Lamphear, B. J., R. Kirchweger, T. Skern, and R. E. Rhoads. 1995. 'Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation', Journal of Biological Chemistry, 270: 21975-83.
Landry, D. M., M. I. Hertz, and S. R. Thompson. 2009. 'RPS25 is essential for translation initiation by the Dicistroviridae and hepatitis C viral IRESs', Genes and Development, 23: 2753-64.
Lee, Pin-Tse, Po-Kuan Chao, Li-Chin Ou, Jian-Ying Chuang, Yen-Chang Lin, Shu-Chun Chen, Hsiao-Fu Chang, Ping-Yee Law, Horace H. Loh, Yu-Sheng Chao, Tsung-Ping Su, and Shiu-Hwa Yeh. 2014. 'Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling', Nucleic Acids Research, 42: 13012-25.
Lee, S., B. Liu, S. Lee, S. X. Huang, B. Shen, and S. B. Qian. 2012. 'Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution', Proceedings of the National Academy of Sciences of the United States of America, 109: E2424-32.
Liang, H. C., Y. C. Liu, H. Chen, M. C. Ku, Q. T. Do, C. Y. Wang, S. F. Tzeng, and S. H. Chen. 2018. 'In Situ Click Reaction Coupled with Quantitative Proteomics for Identifying Protein Targets of Catechol Estrogens', Journal of Proteome Research, 17: 2590-99.
Liberman, Noa, Valentina Gandin, Yuri V. Svitkin, Maya David, Geneviève Virgili, Maritza Jaramillo, Martin Holcik, Bhushan Nagar, Adi Kimchi, and Nahum Sonenberg. 2015. 'DAP5 associates with eIF2β and eIF4AI to promote Internal Ribosome Entry Site driven translation', Nucleic Acids Research, 43: 3764-75.
Lin, J. Y., M. L. Li, P. N. Huang, K. Y. Chien, J. T. Horng, and S. R. Shih. 2008. 'Heterogeneous nuclear ribonuclear protein K interacts with the enterovirus 71 5' untranslated region and participates in virus replication', Journal of General Virology, 89: 2540-9.
Lin, Y. M., C. C. Tsai, C. L. Chung, P. R. Chen, H. S. Sun, S. J. Tsai, and B. M. Huang. 2010. 'Fibroblast growth factor 9 stimulates steroidogenesis in postnatal Leydig cells', International Journal of Andrology, 33: 545-53.
Lloyd, R. E. 2006. 'Translational control by viral proteinases', Virus Research, 119: 76-88.
Macejak, D. G., and P. Sarnow. 1991. 'Internal initiation of translation mediated by the 5' leader of a cellular mRNA', Nature, 353: 90-4.
Mailliot, J., and F. Martin. 2018. 'Viral internal ribosomal entry sites: four classes for one goal', Wiley Interdiscip Rev RNA, 9.
Majzoub, Karim, Mohamed Lamine Hafirassou, Carine Meignin, Akira Goto, Stefano Marzi, Antonina Fedorova, Yann Verdier, Joëlle Vinh, Jules A Hoffmann, Franck Martin, Thomas F Baumert, Catherine Schuster, and Jean-Luc Imler. 2014. 'RACK1 Controls IRES-Mediated Translation of Viruses', Cell, 159: 1086-95.
Meyer, K. D., D. P. Patil, J. Zhou, A. Zinoviev, M. A. Skabkin, O. Elemento, T. V. Pestova, S. B. Qian, and S. R. Jaffrey. 2015. '5' UTR m(6)A Promotes Cap-Independent Translation', Cell, 163: 999-1010.
Miyamoto, M., K. Naruo, C. Seko, S. Matsumoto, T. Kondo, and T. Kurokawa. 1993. 'Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property', Molecular and Cellular Biology, 13: 4251-9.
Mizukami, T., Y. Togashi, S. Naruki, E. Banno, M. Terashima, M. A. de Velasco, K. Sakai, A. Yoneshige, H. Hayashi, Y. Fujita, S. Tomida, T. E. Nakajima, T. Fujino, N. Boku, A. Ito, K. Nakagawa, and K. Nishio. 2017. 'Significance of FGF9 gene in resistance to anti-EGFR therapies targeting colorectal cancer: A subset of colorectal cancer patients with FGF9 upregulation may be resistant to anti-EGFR therapies', Molecular Carcinogenesis, 56: 106-17.
Mokrejs, M., T. Masek, V. Vopalensky, P. Hlubucek, P. Delbos, and M. Pospisek. 2010. 'IRESite--a tool for the examination of viral and cellular internal ribosome entry sites', Nucleic Acids Research, 38: D131-6.
Moore, N. F., A. Kearns, and J. S. Pullin. 1980. 'Characterization of cricket paralysis virus-induced polypeptides in Drosophila cells', Journal of Virology, 33: 1-9.
Muhs, M., T. Hilal, T. Mielke, M. A. Skabkin, K. Y. Sanbonmatsu, T. V. Pestova, and C. M. Spahn. 2015. 'Cryo-EM of ribosomal 80S complexes with termination factors reveals the translocated cricket paralysis virus IRES', Molecular Cell, 57: 422-32.
Murray, J., C. G. Savva, B. S. Shin, T. E. Dever, V. Ramakrishnan, and I. S. Fernandez. 2016. 'Structural characterization of ribosome recruitment and translocation by type IV IRES', Elife, 5.
Nyamao, R. M., J. Wu, L. Yu, X. Xiao, and F. M. Zhang. 2019. 'Roles of DDX5 in the tumorigenesis, proliferation, differentiation, metastasis and pathway regulation of human malignancies', Biochim Biophys Acta Rev Cancer, 1871: 85-98.
Ornitz, D. M., and N. Itoh. 2015. 'The Fibroblast Growth Factor signaling pathway', Wiley Interdiscip Rev Dev Biol, 4: 215-66.
Ornitz, D. M., J. Xu, J. S. Colvin, D. G. McEwen, C. A. MacArthur, F. Coulier, G. Gao, and M. Goldfarb. 1996. 'Receptor specificity of the fibroblast growth factor family', Journal of Biological Chemistry, 271: 15292-7.
Pelletier, J., and N. Sonenberg. 1988. 'Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA', Nature, 334: 320-5.
Petz, Michaela, Nicole Them, Heidemarie Huber, Hartmut Beug, and Wolfgang Mikulits. 2011. 'La enhances IRES-mediated translation of laminin B1 during malignant epithelial to mesenchymal transition', Nucleic Acids Research, 40: 290-302.
Piccirillo, C. A., E. Bjur, I. Topisirovic, N. Sonenberg, and O. Larsson. 2014. 'Translational control of immune responses: from transcripts to translatomes', Nature Immunology, 15: 503-11.
Plank, T. D., and J. S. Kieft. 2012. 'The structures of nonprotein-coding RNAs that drive internal ribosome entry site function', Wiley Interdiscip Rev RNA, 3: 195-212.
Ren, C., H. Chen, C. Han, D. Fu, F. Wang, D. Wang, L. Ma, L. Zhou, and D. Han. 2016. 'The anti-apoptotic and prognostic value of fibroblast growth factor 9 in gastric cancer', Oncotarget, 7: 36655-65.
Robinson, D., A. Hasharoni, Z. Evron, M. Segal, and Z. Nevo. 2000. 'Synovial chondromatosis: the possible role of FGF 9 and FGF receptor 3 in its pathology', International Journal of Experimental Pathology, 81: 183-9.
Ríos-Marco, Pablo, Cristina Romero-López, and Alfredo Berzal-Herranz. 2016. 'The cis-acting replication element of the Hepatitis C virus genome recruits host factors that influence viral replication and translation', Scientific Reports, 6: 25729.
Sato, S., M. Idogawa, K. Honda, G. Fujii, H. Kawashima, K. Takekuma, A. Hoshika, S. Hirohashi, and T. Yamada. 2005. 'Beta-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing', Gastroenterology, 129: 1225-36.
Schepens, B., S. A. Tinton, Y. Bruynooghe, R. Beyaert, and S. Cornelis. 2005. 'The polypyrimidine tract-binding protein stimulates HIF-1alpha IRES-mediated translation during hypoxia', Nucleic Acids Research, 33: 6884-94.
Seo, M., and K. Noguchi. 1995. 'Retinoic acid induces gene expression of fibroblast growth factor-9 during induction of neuronal differentiation of mouse embryonal carcinoma P19 cells', FEBS Letters, 370: 231-5.
Sonenberg, N., and A. G. Hinnebusch. 2009. 'Regulation of translation initiation in eukaryotes: mechanisms and biological targets', Cell, 136: 731-45.
Song, J., and J. M. Slack. 1996. 'XFGF-9: a new fibroblast growth factor from Xenopus embryos', Developmental Dynamics, 206: 427-36.
Steffen, Kristan K., Mark A. McCormick, Kim M. Pham, Vivian L. MacKay, Joe R. Delaney, Christopher J. Murakami, Matt Kaeberlein, and Brian K. Kennedy. 2012. 'Ribosome Deficiency Protects Against ER Stress in <em>Saccharomyces cerevisiae</em>', Genetics, 191: 107-18.
Stein, I., A. Itin, P. Einat, R. Skaliter, Z. Grossman, and E. Keshet. 1998. 'Translation of vascular endothelial growth factor mRNA by internal ribosome entry: implications for translation under hypoxia', Molecular and Cellular Biology, 18: 3112-9.
Todo, T., T. Kondo, S. Nakamura, T. Kirino, T. Kurokawa, and K. Ikeda. 1998. 'Neuronal localization of fibroblast growth factor-9 immunoreactivity in human and rat brain', Brain Research, 783: 179-87.
Tsai, S. J., M. H. Wu, H. M. Chen, P. C. Chuang, and L. Y. Wing. 2002. 'Fibroblast growth factor-9 is an endometrial stromal growth factor', Endocrinology, 143: 2715-21.
Uniacke, J., C. E. Holterman, G. Lachance, A. Franovic, M. D. Jacob, M. R. Fabian, J. Payette, M. Holcik, A. Pause, and S. Lee. 2012. 'An oxygen-regulated switch in the protein synthesis machinery', Nature, 486: 126-9.
Vaklavas, C., K. R. Zinn, S. L. Samuel, Z. Meng, W. E. Grizzle, H. Choi, and S. W. Blume. 2018. 'Translational control of the undifferentiated phenotype in ERpositive breast tumor cells: Cytoplasmic localization of ERalpha and impact of IRES inhibition', Oncology Reports, 39: 2482-98.
Walsh, D., and I. Mohr. 2011. 'Viral subversion of the host protein synthesis machinery', Nature Reviews: Microbiology, 9: 860-75.
Wang, S., Y. Li, C. Jiang, and H. Tian. 2018. 'Fibroblast growth factor 9 subfamily and the heart', Applied Microbiology and Biotechnology, 102: 605-13.
Weingarten-Gabbay, S., D. Khan, N. Liberman, Y. Yoffe, S. Bialik, S. Das, M. Oren, and A. Kimchi. 2013. 'The translation initiation factor DAP5 promotes IRES-driven translation of p53 mRNA', Oncogene, 33: 611.
White, A. C., K. J. Lavine, and D. M. Ornitz. 2007. 'FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network', Development, 134: 3743-52.
Wilson, J. E., T. V. Pestova, C. U. Hellen, and P. Sarnow. 2000. 'Initiation of protein synthesis from the A site of the ribosome', Cell, 102: 511-20.
Wing, L. Y., P. C. Chuang, M. H. Wu, H. M. Chen, and S. J. Tsai. 2003. 'Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen', Journal of Clinical Endocrinology and Metabolism, 88: 5547-54.
Wouters, B. G., and M. Koritzinsky. 2008. 'Hypoxia signalling through mTOR and the unfolded protein response in cancer', Nature Reviews: Cancer, 8: 851-64.
Zhang, Haojian, Huawei Li, Hualin S. Xi, and Shaoguang Li. 2012. 'HIF1α is required for survival maintenance of chronic myeloid leukemia stem cells', Blood, 119: 2595-607.
Zhou, J., J. Wan, X. E. Shu, Y. Mao, X. M. Liu, X. Yuan, X. Zhang, M. E. Hess, J. C. Bruning, and S. B. Qian. 2018. 'N(6)-Methyladenosine Guides mRNA Alternative Translation during Integrated Stress Response', Molecular Cell, 69: 636-47 e7.
Zhu, Yumin, Gang Xu, Yucheng T Yang, Zhiyu Xu, Xinduo Chen, Binbin Shi, Daoxin Xie, Zhi John Lu, and Pengyuan Wang. 2018. 'POSTAR2: deciphering the post-transcriptional regulatory logics', Nucleic Acids Research, 47: D203-D11.