The role of the DEAD-box RNA helicase DDX3 in mRNA metabolism

Wiley Interdisciplinary Reviews: RNA

Volumn 4, Issue 4, 2013, Pages 369-385

  Soto Rifo, Ricardo ^a   Ohlmann, Théophile ^b,c,d  

^a UNIVERSITY OF CHILE   (Chile)

^b CENTRE INTERNATIONAL DE RECHERCHE EN INFECTIOLOGIE   (France)

^c UNIVERSITÉ DE LYON   (France)

^d CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

DDX3 PROTEIN; DEAD BOX PROTEIN; MESSENGER RNA; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL GRANULE; COMPLEX FORMATION; CYTOPLASM; ENZYME STRUCTURE; EXON; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; NUCLEAR EXPORT SIGNAL; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; RNA METABOLISM; TRANSLATION INITIATION; TRANSLATION REGULATION; VIRUS REPLICATION;

DEAD-BOX RNA HELICASES; HUMANS; RNA, MESSENGER;

EID: 84879132779     PISSN: 17577004     EISSN: 17577012     Source Type: Journal    
DOI: 10.1002/wrna.1165     Document Type: Article

References (115)

1. Robertson MP, Joyce GF. The origins of the RNA world. Cold Spring Harb Perspect Biol 2012, 4(5).
2. Cech TR. The RNA worlds in context. Cold Spring Harb Perspect Biol 2012, 4:a006742.
3. Li PT, Vieregg J, Tinoco I Jr. How RNA unfolds and refolds. Annu Rev Biochem 2008, 77:77-100.
4. Lahn BT, Page DC. Functional coherence of the human Y chromosome. Science 1997, 278:675-680.
5. Park SH, Lee SG, Kim Y, Song K. Assignment of a human putative RNA helicase gene, DDX3, to human X chromosome bands p11.3-p11.23. Cytogenet Cell Genet 1998, 81:178-179.
6. Foresta C, Ferlin A, Moro E. Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility. Hum Mol Genet 2000, 9:1161-1169.
7. Linder P, Jankowsky E. From unwinding to clamping-the DEAD box RNA helicase family. Nat Rev Mol Cell Biol 2011, 12:505-516.
8. Linder P, Lasko PF, Ashburner M, Leroy P, Nielsen PJ, Nishi K, Schnier J, Slonimski PP. Birth of the D-E-A-D box. Nature 1989, 337:121-122. Erratum in: Nature 1989, 340:246.
9. Yedavalli VS, Neuveut C, Chi YH, Kleiman L, Jeang KT. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell 2004, 119:381-392.
10. Franca R, Belfiore A, Spadari S, Maga G. Human DEAD-box ATPase DDX3 shows a relaxed nucleoside substrate specificity. Proteins 2007, 67:1128-1137.
11. Hogbom M, Collins R, van den Berg S, Jenvert RM, Karlberg T, Kotenyova T, Flores A, Karlsson Hedestam GB, Schiavone LH. Crystal structure of conserved domains 1 and 2 of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP. J Mol Biol 2007, 372:150-159.
12. Jankowsky E. RNA helicases at work: binding and rearranging. Trends Biochem Sci 2011, 36:19-29.
13. Jankowsky E, Bowers H. Remodeling of ribonucleoprotein complexes with DExH/D RNA helicases. Nucleic Acids Res 2006, 34:4181-4188.
14. Russell R, Jarmoskaite I, Lambowitz AM. Toward a molecular understanding of RNA remodeling by DEAD-box proteins. RNA Biol 2012, 10(1):44-55.
15. Jarmoskaite I, Russell R. DEAD-box proteins as RNA helicases and chaperones. Wiley Interdiscip Rev RNA 2011, 2:135-152.
16. Singleton MR, Dillingham MS, Wigley DB. Structure and mechanism of helicases and nucleic acid translocases. Annu Rev Biochem 2007, 76:23-50.
17. Pyle AM. RNA helicases and remodeling proteins. Curr Opin Chem Biol 2011, 15:636-642.
18. Lohman TM, Tomko EJ, Wu CG. Non-hexameric DNA helicases and translocases: mechanisms and regulation. Nat Rev Mol Cell Biol 2008, 9:391-401.
19. Myong S, Ha T. Stepwise translocation of nucleic acid motors. Curr Opin Struct Biol 2010, 20:121-127.
20. Pyle AM. Translocation and unwinding mechanisms of RNA and DNA helicases. Annu Rev Biophys 2008, 37:317-336.
21. Schroder M. Human DEAD-box protein 3 has multiple functions in gene regulation and cell cycle control and is a prime target for viral manipulation. Biochem Pharmacol 2010, 79:297-306.
22. Schroder M. Viruses and the human DEAD-box helicase DDX3: inhibition or exploitation? Biochem Soc Trans 2011, 39:679-683.
23. Lai MC, Lee YH, Tarn WY. The DEAD-box RNA helicase DDX3 associates with export messenger ribonucleoproteins as well as tip-associated protein and participates in translational control. Mol Biol Cell 2008, 19:3847-3858.
24. Lee CS, Dias AP, Jedrychowski M, Patel AH, Hsu JL, Reed R. Human DDX3 functions in translation and interacts with the translation initiation factor eIF3. Nucleic Acids Res 2008, 36:4708-4718.
25. Soto-Rifo R, Rubilar PS, Limousin T, de Breyne S, Decimo D, Ohlmann T. DEAD-box protein DDX3 associates with eIF4F to promote translation of selected mRNAs. EMBO J 2012, 31:3745-3756.
26. Schroder M, Baran M, Bowie AG. Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKε-mediated IRF activation. EMBO J 2008, 27:2147-2157.
27. Tarn WY, Chang TH. The current understanding of Ded1p/DDX3 homologs from yeast to human. RNA Biol 2009, 6:17-20.
28. Rosner A, Rinkevich B. The DDX3 subfamily of the DEAD box helicases: divergent roles as unveiled by studying different organisms and in vitro assays. Curr Med Chem 2007, 14:2517-2525.
29. Fairman-Williams ME, Guenther UP, Jankowsky E. SF1 and SF2 helicases: family matters. Curr Opin Struct Biol 2010, 20:313-324.
30. Jankowsky A, Guenther UP, Jankowsky E. The RNA helicase database. Nucleic Acids Res 2011, 39:D338-D341.
31. Cordin O, Banroques J, Tanner NK, Linder P. The DEAD-box protein family of RNA helicases. Gene 2006, 367:17-37.
32. Bowers HA, Maroney PA, Fairman ME, Kastner B, Luhrmann R, Nilsen TW, Jankowsky E. Discriminatory RNP remodeling by the DEAD-box protein DED1. RNA 2006, 12:903-912.
33. Yang Q, Del Campo M, Lambowitz AM, Jankowsky E. DEAD-box proteins unwind duplexes by local strand separation. Mol Cell 2007, 28:253-263.
34. Yang Q, Jankowsky E. The DEAD-box protein Ded1 unwinds RNA duplexes by a mode distinct from translocating helicases. Nat Struct Mol Biol 2006, 13:981-986.
35. Liu F, Putnam A, Jankowsky E. ATP hydrolysis is required for DEAD-box protein recycling but not for duplex unwinding. Proc Natl Acad Sci U S A 2008, 105:20209-20214.
36. Chen Y, Potratz JP, Tijerina P, Del Campo M, Lambowitz AM, Russell R. DEAD-box proteins can completely separate an RNA duplex using a single ATP. Proc Natl Acad Sci U S A 2008, 105:20203-20208.
37. Bono F, Ebert J, Lorentzen E, Conti E. The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA. Cell 2006, 126:713-725.
38. Ballut L, Marchadier B, Baguet A, Tomasetto C, Seraphin B, Le Hir H. The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Nat Struct Mol Biol 2005, 12:861-869.
39. Sengoku T, Nureki O, Nakamura A, Kobayashi S, Yokoyama S. Structural basis for RNA unwinding by the DEAD-box protein Drosophila Vasa. Cell 2006, 125:287-300.
40. Tanner NK, Linder P. DExD/H box RNA helicases: from generic motors to specific dissociation functions. Mol Cell 2001, 8:251-262.
41. Garbelli A, Beermann S, Di Cicco G, Dietrich U, Maga G. A motif unique to the human DEAD-box protein DDX3 is important for nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication. PLoS One 2011, 6:e19810.
42. Shih JW, Tsai TY, Chao CH, Wu Lee YH. Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein. Oncogene 2008, 27:700-714.
43. Shih JW, Wang WT, Tsai TY, Kuo CY, Li HK, Wu Lee YH. Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response. Biochem J 2011, 1:119-129.
44. Chao CH, Chen CM, Cheng PL, Shih JW, Tsou AP, Lee YH. DDX3, a DEAD box RNA helicase with tumor growth-suppressive property and transcriptional regulation activity of the p21waf1/cip1 promoter, is a candidate tumor suppressor. Cancer Res 2006, 66:6579-6588.
45. Moore MJ. From birth to death: the complex lives of eukaryotic mRNAs. Science 2005, 309:1514-1518.
46. Moore MJ, Proudfoot NJ. Pre-mRNA processing reaches back to transcription and ahead to translation. Cell 2009, 136:688-700.
47. Bregman A, Avraham-Kelbert M, Barkai O, Duek L, Guterman A, Choder M. Promoter elements regulate cytoplasmic mRNA decay. Cell 2011, 147:1473-1483.
48. Trcek T, Larson DR, Moldon A, Query CC, Singer RH. Single-molecule mRNA decay measurements reveal promoter- regulated mRNA stability in yeast. Cell 2011, 147:1484-1497.
49. Dahan N, Choder M. The eukaryotic transcriptional machinery regulates mRNA translation and decay in the cytoplasm. Biochim Biophys Acta 2013, 1829:169-173.
50. Han J, Xiong J, Wang D, Fu XD. Pre-mRNA splicing: where and when in the nucleus. Trends Cell Biol 2011, 21:336-343.
51. Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5′ end of mRNA. Cell 2006, 127:1389-1400.
52. Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev 2005, 19:1512-1517.
53. Le Hir H, Nott A, Moore MJ. How introns influence and enhance eukaryotic gene expression. Trends Biochem Sci 2003, 28:215-220.
54. Le Hir H, Seraphin B. EJCs at the heart of translational control. Cell 2008, 133:213-216.
55. Nott A, Le Hir H, Moore MJ. Splicing enhances translation in mammalian cells: an additional function of the exon junction complex. Genes Dev 2004, 18:210-222.
56. Le Hir H, Gatfield D, Izaurralde E, Moore MJ. The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J 2001, 20:4987-4997.
57. Chang DD, Sharp PA. Regulation by HIV Rev depends upon recognition of splice sites. Cell 1989, 59:789-795.
58. Legrain P, Rosbash M. Some cis- and trans-acting mutants for splicing target pre-mRNA to the cytoplasm. Cell 1989, 57:573-583.
59. Soulat D, Burckstummer T, Westermayer S, Goncalves A, Bauch A, Stefanovic A, Hantschel O, Bennett KL, Decker T, Superti-Furga G. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J 2008, 27:2135-2146.
60. Oshiumi H, Sakai K, Matsumoto M, Seya T. DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN-β-inducing potential. Eur J Immunol 2010, 40:940-948.
61. Botlagunta M, Vesuna F, Mironchik Y, Raman A, Lisok A, Winnard P Jr, Mukadam S, Van Diest P, Chen JH, Farabaugh P et al. Oncogenic role of DDX3 in breast cancer biogenesis. Oncogene 2008, 27:3912-3922.
62. Zhou Z, Licklider LJ, Gygi SP, Reed R. Comprehensive proteomic analysis of the human spliceosome. Nature 2002, 419:182-185.
63. Merz C, Urlaub H, Will CL, Luhrmann R. Protein composition of human mRNPs spliced in vitro and differential requirements for mRNP protein recruitment. RNA 2007, 13:116-128.
64. Topisirovic I, Siddiqui N, Lapointe VL, Trost M, Thibault P, Bangeranye C, Pinol-Roma S, Borden KL. Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP. EMBO J 2009, 28:1087-1098.
65. Culjkovic B, Topisirovic I, Skrabanek L, Ruiz-Gutierrez M, Borden KL. eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR. J Cell Biol 2005, 169:245-256.
66. Culjkovic B, Topisirovic I, Skrabanek L, Ruiz-Gutierrez M, Borden KL. eIF4E is a central node of an RNA regulon that governs cellular proliferation. J Cell Biol 2006, 175:415-426.
67. Pollard VW, Malim MH. The HIV-1 Rev protein. Annu Rev Microbiol 1998, 52:491-532.
68. Cullen BR. Nuclear mRNA export: insights from virology. Trends Biochem Sci 2003, 28:419-424.
69. Weirich CS, Erzberger JP, Flick JS, Berger JM, Thorner J, Weis K. Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. Nat Cell Biol 2006, 8:668-676.
70. Alcazar-Roman AR, Tran EJ, Guo S, Wente SR. Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. Nat Cell Biol 2006, 8:711-716.
71. Naji S, Ambrus G, Cimermancic P, Reyes JR, Johnson JR, Filbrandt R, Huber MD, Vesely P, Krogan NJ, Yates JR, 3rd et al. Host cell interactome of HIV-1 Rev includes RNA helicases involved in multiple facets of virus production. Mol Cell Proteomics 2012, 11:M111.015313.
72. Monette A, Pante N, Mouland AJ. HIV-1 remodels the nuclear pore complex. J Cell Biol 2011, 193:619-631.
73. Chuang RY, Weaver PL, Liu Z, Chang TH. Requirement of the DEAD-Box protein ded1p for messenger RNA translation. Science 1997, 275:1468-1471.
74. de la Cruz J, Iost I, Kressler D, Linder P. The p20 and Ded1 proteins have antagonistic roles in eIF4E-dependent translation in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 1997, 94:5201-5206.
75. Mamiya N, Worman HJ. Hepatitis C virus core protein binds to a DEAD box RNA helicase. J Biol Chem 1999, 274:15751-15756.
76. Geissler R, Golbik RP, Behrens SE. The DEAD-box helicase DDX3 supports the assembly of functional 80S ribosomes. Nucleic Acids Res 2012, 40:4998-5011.
77. Fukumura J, Noguchi E, Sekiguchi T, Nishimoto T. A temperature-sensitive mutant of the mammalian RNA helicase, DEAD-BOX X isoform, DBX, defective in the transition from G1 to S phase. J Biochem 2003, 134:71-82.
78. Lai MC, Chang WC, Shieh SY, Tarn WY. DDX3 regulates cell growth through translational control of cyclin E1. Mol Cell Biol 2010, 30:5444-5453.
79. Beckham C, Hilliker A, Cziko AM, Noueiry A, Ramaswami M, Parker R. The DEAD-box RNA helicase Ded1p affects and accumulates in Saccharomyces cerevisiae P-bodies. Mol Biol Cell 2008, 19:984-993.
80. Hilliker A, Gao Z, Jankowsky E, Parker R. The DEAD-box protein Ded1 modulates translation by the formation and resolution of an eIF4F-mRNA complex. Mol Cell 2011, 43:962-972.
81. Abaeva IS, Marintchev A, Pisareva VP, Hellen CU, Pestova TV. Bypassing of stems versus linear base-by-base inspection of mammalian mRNAs during ribosomal scanning. EMBO J 2011, 30:115-129.
82. Marsden S, Nardelli M, Linder P, McCarthy JE. Unwinding single RNA molecules using helicases involved in eukaryotic translation initiation. J Mol Biol 2006, 361:327-335.
83. Berthelot K, Muldoon M, Rajkowitsch L, Hughes J, McCarthy JE. Dynamics and processivity of 40S ribosome scanning on mRNA in yeast. Mol Microbiol 2004, 51:987-1001.
84. Soto-Rifo R, Limousin T, Rubilar PS, Ricci EP, Decimo D, Moncorge O, Trabaud MA, Andre P, Cimarelli A, Ohlmann T. Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation. Nucleic Acids Res 2012, 1:2653-2667.
85. Parkin NT, Cohen EA, Darveau A, Rosen C, Haseltine W, Sonenberg N. Mutational analysis of the 5′ non-coding region of human immunodeficiency virus type 1: effects of secondary structure on translation. EMBO J 1988, 7:2831-2837.
86. Anderson P, Kedersha N. RNA granules. J Cell Biol 2006, 172:803-808.
87. Anderson P, Kedersha N. RNA granules: post-transcriptional and epigenetic modulators of gene expression. Nat Rev Mol Cell Biol 2009, 10:430-436.
88. Martin KC, Ephrussi A. mRNA localization: gene expression in the spatial dimension. Cell 2009, 136:719-730.
89. Anderson P, Kedersha N. Stress granules: the Tao of RNA triage. Trends Biochem Sci 2008, 33:141-150.
90. Eulalio A, Behm-Ansmant I, Izaurralde E. P bodies: at the crossroads of post-transcriptional pathways. Nat Rev Mol Cell Biol 2007, 8:9-22.
91. Kanai Y, Dohmae N, Hirokawa N. Kinesin transports RNA: isolation and characterization of an RNA-transporting granule. Neuron 2004, 43:513-525.
92. Elvira G, Wasiak S, Blandford V, Tong XK, Serrano A, Fan X, del Rayo Sanchez-Carbente M, Servant F, Bell AW, Boismenu D et al. Characterization of an RNA granule from developing brain. Mol Cell Proteomics 2006, 5:635-651.
93. Chahar HS, Chen S, Manjunath N. P-body components LSM1, GW182, DDX3, DDX6 and XRN1 are recruited to WNV replication sites and positively regulate viral replication. Virology 2013, 436:1-7.
94. Owsianka AM, Patel AH. Hepatitis C virus core protein interacts with a human DEAD box protein DDX3. Virology 1999, 257:330-340.
95. You LR, Chen CM, Yeh TS, Tsai TY, Mai RT, Lin CH, Lee YH. Hepatitis C virus core protein interacts with cellular putative RNA helicase. J Virol 1999, 73:2841-2853.
96. Angus AG, Dalrymple D, Boulant S, McGivern DR, Clayton RF, Scott MJ, Adair R, Graham S, Owsianka AM, Targett-Adams P et al. Requirement of cellular DDX3 for hepatitis C virus replication is unrelated to its interaction with the viral core protein. J Gen Virol 2010, 91:122-132.
97. Ariumi Y, Kuroki M, Abe K, Dansako H, Ikeda M, Wakita T, Kato N. DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication. J Virol 2007, 81:13922-13926.
98. Kang JI, Kwon YC, Ahn BY. Modulation of the type I interferon pathways by culture-adaptive hepatitis C virus core mutants. FEBS Lett 2012, 586:1272-1278.
99. Oshiumi H, Ikeda M, Matsumoto M, Watanabe A, Takeuchi O, Akira S, Kato N, Shimotohno K, Seya T. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-β induction. PLoS One 2010, 5:e14258.
100. Wang H, Ryu WS. Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion. PLoS Pathog 2010, 6:e1000986.
101. Vashist S, Urena L, Chaudhry Y, Goodfellow I. Identification of RNA-protein interaction networks involved in the norovirus life cycle. J Virol 2012, 86:11977-11990.
102. Molina H, Horn DM, Tang N, Mathivanan S, Pandey A. Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci U S A 2007, 104:2199-2204.
103. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ. Immunoaffi{ligature}nity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol 2005, 23:94-101.
104. Tao WA, Wollscheid B, O'Brien R, Eng JK, Li XJ, Bodenmiller B, Watts JD, Hood L, Aebersold R. Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry. Nat Methods 2005, 2:591-598.
105. Yu LR, Issaq HJ, Veenstra TD. Phosphoproteomics for the discovery of kinases as cancer biomarkers and drug targets. Proteomics Clin Appl 2007, 1:1042-1057.
106. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP. A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 2008, 105:10762-10767.
107. Choi YJ, Lee SG. The DEAD-box RNA helicase DDX3 interacts with DDX5, co-localizes with it in the cytoplasm during the G2/M phase of the cycle, and affects its shuttling during mRNP export. J Cell Biochem 2012, 113:985-996.
108. Jones DT, Lechertier T, Mitter R, Herbert JM, Bicknell R, Jones JL, Li JL, Buffa F, Harris AL, Hodivala-Dilke K. Gene expression analysis in human breast cancer associated blood vessels. PLoS One 2012, 7:e44294.
109. Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J, Carneiro MO, Carter SL, Cibulskis K, Erlich RL et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 2012, 488:106-110.
110. Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, Phoenix TN, Hedlund E, Wei L, Zhu X et al. Novel mutations target distinct subgroups of medulloblastoma. Nature 2012, 488:43-48.
111. Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A et al. The mutational landscape of head and neck squamous cell carcinoma. Science 2011, 333:1157-1160.
112. Wu DW, Liu WS, Wang J, Chen CY, Cheng YW, Lee H. Reduced p21(WAF1/CIP1) via alteration of p53-DDX3 pathway is associated with poor relapse-free survival in early-stage human papillomavirus-associated lung cancer. Clin Cancer Res 2011, 17:1895-1905.
113. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, Werner L, Sivachenko A, DeLuca DS, Zhang L et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011, 365:2497-2506.
114. Chang PC, Chi CW, Chau GY, Li FY, Tsai YH, Wu JC, Wu Lee YH. DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control. Oncogene 2006, 25:1991-2003.
115. Maga G, Falchi F, Radi M, Botta L, Casaluce G, Bernardini M, Irannejad H, Manetti F, Garbelli A, Samuele A et al. Toward the discovery of novel anti-HIV drugs. Second-generation inhibitors of the cellular ATPase DDX3 with improved anti-HIV activity: synthesis, structure-activity relationship analysis, cytotoxicity studies, and target validation. ChemMedChem 2011, 6:1371-1389.