Disease caused by dengue virus is a global health concern with up to 390 million individuals infected annually worldwide. There are no vaccines or antiviral compounds available to either prevent or treat dengue disease which may be fatal. To increase our understanding of the interaction of dengue virus with the host cell, we analyzed changes in the proteome of human A549 cells in response to dengue virus type 2 infection using stable isotope labelling in cell culture (SILAC) in combination with high-throughput mass spectrometry (MS). Mock and infected A549 cells were fractionated into nuclear and cytoplasmic extracts before analysis to identify proteins that redistribute between cellular compartments during infection and reduce the complexity of the analysis. We identified and quantified 3098 and 2115 proteins in the cytoplasmic and nuclear fractions respectively. Proteins that showed a significant alteration in amount during infection were examined using gene enrichment, pathway and network analysis tools. The analyses revealed that dengue virus infection modulated the amounts of proteins involved in the interferon and unfolded protein responses, lipid metabolism and the cell cycle. The SILAC-MS results were validated for a select number of proteins over a time course of infection by Western blotting and immunofluorescence microscopy. Our study demonstrates for the first time the power of SILAC-MS for identifying and quantifying novel changes in cellular protein amounts in response to dengue virus infection.
References
[1]
WHO (2009) Dengue - Guidelines for diagnosis, Treatment, prevention and control. WHO Press.
[2]
Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, et al. (2013) The global distribution and burden of dengue. Nature 496: 504–507. doi: 10.1038/nature12060
[3]
Lindenbach BD, Thiel HJ, Rice CM (2007) Flaviviridae: the viruses and their replication. In: Knipe DM, Howley PM, editors. Fields Virology, 5th Edition. Philadelphia: Lippincott-Raven Publishers. pp. 1101–1152.
[4]
Welsch S, Miller S, Romero-Brey I, Merz A, Bleck CK, et al. (2009) Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5: 365–375. doi: 10.1016/j.chom.2009.03.007
[5]
Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, et al. (2008) RNA interference screen for human genes associated with West Nile virus infection. Nature 455: 242–245. doi: 10.1038/nature07207
[6]
Sessions OM, Barrows NJ, Souza-Neto JA, Robinson TJ, Hershey CL, et al. (2009) Discovery of insect and human dengue virus host factors. Nature 458: 1047–1050. doi: 10.1038/nature07967
[7]
Balas C, Kennel A, Deauvieau F, Sodoyer R, Arnaud-Barbe N, et al. (2011) Different innate signatures induced in human monocyte-derived dendritic cells by wild-type dengue 3 virus, attenuated but reactogenic dengue 3 vaccine virus, or attenuated nonreactogenic dengue 1–4 vaccine virus strains. J Infect Dis 203: 103–108. doi: 10.1093/infdis/jiq022
[8]
Fink J, Gu F, Ling L, Tolfvenstam T, Olfat F, et al. (2007) Host gene expression profiling of dengue virus infection in cell lines and patients. PLoS Negl Trop Dis 1: e86. doi: 10.1371/journal.pntd.0000086
[9]
Sessions OM, Tan Y, Goh KC, Liu Y, Tan P, et al. (2013) Host cell transcriptome profile during wild-type and attenuated dengue virus infection. PLoS Negl Trop Dis 7: e2107. doi: 10.1371/journal.pntd.0002107
[10]
Silveira GF, Meyer F, Delfraro A, Mosimann AL, Coluchi N, et al. (2011) Dengue virus type 3 isolated from a fatal case with visceral complications induces enhanced proinflammatory responses and apoptosis of human dendritic cells. J Virol 85: 5374–5383. doi: 10.1128/jvi.01915-10
[11]
Ubol S, Masrinoul P, Chaijaruwanich J, Kalayanarooj S, Charoensirisuthikul T, et al. (2008) Differences in global gene expression in peripheral blood mononuclear cells indicate a significant role of the innate responses in progression of dengue fever but not dengue hemorrhagic fever. J Infect Dis 197: 1459–1467. doi: 10.1086/587699
[12]
Warke RV, Martin KJ, Giaya K, Shaw SK, Rothman AL, et al. (2008) TRAIL is a novel antiviral protein against dengue virus. J Virol 82: 555–564. doi: 10.1128/jvi.01694-06
[13]
Warke RV, Xhaja K, Martin KJ, Fournier MF, Shaw SK, et al. (2003) Dengue virus induces novel changes in gene expression of human umbilical vein endothelial cells. J Virol 77: 11822–11832. doi: 10.1128/jvi.77.21.11822-11832.2003
[14]
Devignot S, Sapet C, Duong V, Bergon A, Rihet P, et al. (2010) Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue. PLoS One 5: e11671. doi: 10.1371/journal.pone.0011671
[15]
Hoang LT, Lynn DJ, Henn M, Birren BW, Lennon NJ, et al.. (2010) The early whole-blood transcriptional signature of dengue and features associated with progression to dengue shock syndrome in Vietnamese children and young adults. J Virol.
[16]
Loke P, Hammond SN, Leung JM, Kim CC, Batra S, et al. (2010) Gene expression patterns of dengue virus-infected children from nicaragua reveal a distinct signature of increased metabolism. PLoS Negl Trop Dis 4: e710. doi: 10.1371/journal.pntd.0000710
[17]
Nascimento EJ, Braga-Neto U, Calzavara-Silva CE, Gomes AL, Abath FG, et al. (2009) Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome. PLoS One 4: e7892. doi: 10.1371/journal.pone.0007892
[18]
Simmons CP, Popper S, Dolocek C, Chau TN, Griffiths M, et al. (2007) Patterns of host genome-wide gene transcript abundance in the peripheral blood of patients with acute dengue hemorrhagic fever. J Infect Dis 195: 1097–1107. doi: 10.1086/512162
[19]
Tolfvenstam T, Lindblom A, Schreiber MJ, Ling L, Chow A, et al. (2011) Characterization of early host responses in adults with dengue disease. BMC Infect Dis 11: 209. doi: 10.1186/1471-2334-11-209
[20]
Khadka S, Vangeloff AD, Zhang C, Siddavatam P, Heaton NS, et al.. (2011) A physical interaction network of dengue virus and human proteins. Mol Cell Proteomics.
[21]
Le Breton M, Meyniel-Schicklin L, Deloire A, Coutard B, Canard B, et al. (2011) Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen. BMC Microbiol 11: 234. doi: 10.1186/1471-2180-11-234
[22]
Mairiang D, Zhang H, Sodja A, Murali T, Suriyaphol P, et al. (2013) Identification of new protein interactions between dengue fever virus and its hosts, human and mosquito. PLoS One 8: e53535. doi: 10.1371/journal.pone.0053535
[23]
Kanlaya R, Pattanakitsakul SN, Sinchaikul S, Chen ST, Thongboonkerd V (2009) Alterations in actin cytoskeletal assembly and junctional protein complexes in human endothelial cells induced by dengue virus infection and mimicry of leukocyte transendothelial migration. J Proteome Res 8: 2551–2562. doi: 10.1021/pr900060g
[24]
Kanlaya R, Pattanakitsakul SN, Sinchaikul S, Chen ST, Thongboonkerd V (2010) The Ubiquitin-Proteasome Pathway Is Important for Dengue Virus Infection in Primary Human Endothelial Cells. J Proteome Res.
[25]
Pattanakitsakul SN, Poungsawai J, Kanlaya R, Sinchaikul S, Chen ST, et al. (2010) Association of Alix with late endosomal lysobisphosphatidic acid is important for dengue virus infection in human endothelial cells. J Proteome Res 9: 4640–4648. doi: 10.1021/pr100357f
[26]
Pattanakitsakul SN, Rungrojcharoenkit K, Kanlaya R, Sinchaikul S, Noisakran S, et al. (2007) Proteomic analysis of host responses in HepG2 cells during dengue virus infection. J Proteome Res 6: 4592–4600. doi: 10.1021/pr070366b
[27]
Wati S, Soo ML, Zilm P, Li P, Paton AW, et al. (2009) Dengue virus infection induces upregulation of GRP78, which acts to chaperone viral antigen production. J Virol 83: 12871–12880. doi: 10.1128/jvi.01419-09
[28]
Patramool S, Surasombatpattana P, Luplertlop N, Seveno M, Choumet V, et al. (2011) Proteomic analysis of an Aedes albopictus cell line infected with Dengue serotypes 1 and 3 viruses. Parasit Vectors 4: 138. doi: 10.1186/1756-3305-4-138
[29]
Tchankouo-Nguetcheu S, Khun H, Pincet L, Roux P, Bahut M, et al.. (2010) Differential protein modulation in midguts of Aedes aegypti infected with chikungunya and dengue 2 viruses. PLoS One 5..
[30]
Albuquerque LM, Trugilho MR, Chapeaurouge A, Jurgilas PB, Bozza PT, et al. (2009) Two-dimensional difference gel electrophoresis (DiGE) analysis of plasmas from dengue fever patients. J Proteome Res 8: 5431–5441. doi: 10.1021/pr900236f
[31]
Brasier AR, Garcia J, Wiktorowicz JE, Spratt HM, Comach G, et al. (2012) Discovery Proteomics and Nonparametric Modeling Pipeline in the Development of a Candidate Biomarker Panel for Dengue Hemorrhagic Fever. Clin Transl Sci 5: 8–20. doi: 10.1111/j.1752-8062.2011.00377.x
[32]
Mann M (2006) Functional and quantitative proteomics using SILAC. Nat Rev Mol Cell Biol 7: 952–958. doi: 10.1038/nrm2067
[33]
Walther TC, Mann M (2010) Mass spectrometry-based proteomics in cell biology. J Cell Biol 190: 491–500. doi: 10.1083/jcb.201004052
[34]
Munday DC, Surtees R, Emmott E, Dove BK, Digard P, et al.. (2012) Using SILAC and quantitative proteomics to investigate the interactions between viral and host proteomes. Proteomics.
[35]
Gualano RC, Pryor MJ, Cauchi MR, Wright PJ, Davidson AD (1998) Identification of a major determinant of mouse neurovirulence of dengue virus type 2 using stably cloned genomic-length cDNA. J Gen Virol 79: 437–446.
[36]
Kroschewski H, Lim SP, Butcher RE, Yap TL, Lescar J, et al. (2008) Mutagenesis of the dengue virus type 2 NS5 methyltransferase domain. J Biol Chem 283: 19410–19421. doi: 10.1074/jbc.m800613200
[37]
Cox J, Mann M (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 26: 1367–1372. doi: 10.1038/nbt.1511
[38]
Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, et al. (2011) Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res 10: 1794–1805. doi: 10.1021/pr101065j
[39]
Bhatia VN, Perlman DH, Costello CE, McComb ME (2009) Software tool for researching annotations of proteins: open-source protein annotation software with data visualization. Anal Chem 81: 9819–9823. doi: 10.1021/ac901335x
[40]
Huang da W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44–57. doi: 10.1038/nprot.2008.211
[41]
Huang da W, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37: 1–13. doi: 10.1093/nar/gkn923
[42]
Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, et al. (2013) STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41: D808–815. doi: 10.1093/nar/gks1094
[43]
Hannemann H, Sung PY, Chiu HC, Yousuf A, Bird J, et al.. (2013) Serotype Specific Differences in Dengue Virus Non-Structural Protein 5 Nuclear Localization. J Biol Chem.
[44]
Umareddy I, Tang KF, Vasudevan SG, Devi S, Hibberd ML, et al. (2008) Dengue virus regulates type I interferon signalling in a strain-dependent manner in human cell lines. J Gen Virol 89: 3052–3062. doi: 10.1099/vir.0.2008/001594-0
[45]
Yu CY, Chang TH, Liang JJ, Chiang RL, Lee YL, et al. (2012) Dengue virus targets the adaptor protein MITA to subvert host innate immunity. PLoS Pathog 8: e1002780. doi: 10.1371/journal.ppat.1002780
[46]
Pastorino B, Boucomont-Chapeaublanc E, Peyrefitte CN, Belghazi M, Fusai T, et al.. (2009) Identification of cellular proteome modifications in response to West Nile virus infection. Mol Cell Proteomics.
[47]
Zhang LK, Chai F, Li HY, Xiao G, Guo L (2013) Identification of host proteins involved in Japanese encephalitis virus infection by quantitative proteomics analysis. J Proteome Res 12: 2666–2678. doi: 10.1021/pr400011k
[48]
Munoz-Jordan JL, Bosch I (2010) Modulation of the antiviral response by dengue virus. In: Hanley KA, Weaver SC, editors. Frontiers in Dengue Virus Research: Caister Academic Press. pp. 121–140.
[49]
Chang TH, Liao CL, Lin YL (2006) Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-kappaB activation. Microbes Infect 8: 157–171. doi: 10.1016/j.micinf.2005.06.014
[50]
Marianneau P, Cardona A, Edelman L, Deubel V, Despres P (1997) Dengue virus replication in human hepatoma cells activates NF-kappaB which in turn induces apoptotic cell death. J Virol 71: 3244–3249.
[51]
Pettersson M, Bessonova M, Gu HF, Groop LC, Jonsson JI (2000) Characterization, chromosomal localization, and expression during hematopoietic differentiation of the gene encoding Arl6ip, ADP-ribosylation-like factor-6 interacting protein (ARL6). Genomics 68: 351–354. doi: 10.1006/geno.2000.6278
[52]
Heaton NS, Perera R, Berger KL, Khadka S, Lacount DJ, et al. (2010) Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. Proc Natl Acad Sci U S A 107: 17345–17350. doi: 10.1073/pnas.1010811107
[53]
Diamond DL, Syder AJ, Jacobs JM, Sorensen CM, Walters KA, et al. (2010) Temporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics. PLoS Pathog 6: e1000719. doi: 10.1371/journal.ppat.1000719
[54]
Rasmussen AL, Diamond DL, McDermott JE, Gao X, Metz TO, et al. (2011) Systems virology identifies a mitochondrial fatty acid oxidation enzyme, dodecenoyl coenzyme A delta isomerase, required for hepatitis C virus replication and likely pathogenesis. J Virol 85: 11646–11654. doi: 10.1128/jvi.05605-11
[55]
Pryor MJ, Rawlinson SM, Butcher RE, Barton CL, Waterhouse TA, et al. (2007) Nuclear localization of dengue virus nonstructural protein 5 through its importin alpha/beta-recognized nuclear localization sequences is integral to viral infection. Traffic 8: 795–807. doi: 10.1111/j.1600-0854.2007.00579.x
[56]
Sangiambut S, Keelapang P, Aaskov J, Puttikhunt C, Kasinrerk W, et al. (2008) Multiple regions in dengue virus capsid protein contribute to nuclear localization during virus infection. J Gen Virol 89: 1254–1264. doi: 10.1099/vir.0.83264-0
[57]
Uchil PD, Kumar AV, Satchidanandam V (2006) Nuclear localization of flavivirus RNA synthesis in infected cells. J Virol 80: 5451–5464. doi: 10.1128/jvi.01982-05
[58]
Long HT, Hibberd ML, Hien TT, Dung NM, Van Ngoc T, et al. (2009) Patterns of gene transcript abundance in the blood of children with severe or uncomplicated dengue highlight differences in disease evolution and host response to dengue virus infection. J Infect Dis 199: 537–546. doi: 10.1086/596507
[59]
Jones M, Davidson A, Hibbert L, Gruenwald P, Schlaak J, et al. (2005) Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression. J Virol 79: 5414–5420. doi: 10.1128/jvi.79.9.5414-5420.2005
[60]
Munoz-Jordan JL, Sanchez-Burgos GG, Laurent-Rolle M, Garcia-Sastre A (2003) Inhibition of interferon signaling by dengue virus. Proc Natl Acad Sci U S A 100: 14333–14338. doi: 10.1073/pnas.2335168100
[61]
Diamond MS, Farzan M (2013) The broad-spectrum antiviral functions of IFIT and IFITM proteins. Nat Rev Immunol 13: 46–57. doi: 10.1038/nri3344
[62]
Wacher C, Muller M, Hofer MJ, Getts DR, Zabaras R, et al. (2007) Coordinated regulation and widespread cellular expression of interferon-stimulated genes (ISG) ISG-49, ISG-54, and ISG-56 in the central nervous system after infection with distinct viruses. J Virol 81: 860–871. doi: 10.1128/jvi.01167-06
[63]
Daffis S, Szretter KJ, Schriewer J, Li J, Youn S, et al. (2010) 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature 468: 452–456. doi: 10.1038/nature09489
[64]
Behera B, Chaudhry R, Pandey A, Mohan A, Dar L, et al. (2009) Co-infections due to leptospira, dengue and hepatitis E: a diagnostic challenge. J Infect Dev Ctries 4: 48–50. doi: 10.3855/jidc.535
[65]
Jiang D, Weidner JM, Qing M, Pan XB, Guo H, et al. (2010) Identification of five interferon-induced cellular proteins that inhibit west nile virus and dengue virus infections. J Virol 84: 8332–8341. doi: 10.1128/jvi.02199-09
[66]
Fischl W, Bartenschlager R (2011) Exploitation of cellular pathways by Dengue virus. Curr Opin Microbiol.
[67]
Paradkar PN, Ooi EE, Hanson BJ, Gubler DJ, Vasudevan SG (2010) Unfolded protein response (UPR) gene expression during antibody-dependent enhanced infection of cultured monocytes correlates with dengue disease severity. Biosci Rep.
[68]
Umareddy I, Pluquet O, Wang QY, Vasudevan SG, Chevet E, et al. (2007) Dengue virus serotype infection specifies the activation of the unfolded protein response. Virol J 4: 91. doi: 10.1186/1743-422x-4-91
[69]
Yu CY, Hsu YW, Liao CL, Lin YL (2006) Flavivirus infection activates the XBP1 pathway of the unfolded protein response to cope with endoplasmic reticulum stress. J Virol 80: 11868–11880. doi: 10.1128/jvi.00879-06
[70]
Schussek S, Groves PL, Apte SH, Doolan DL (2013) Highly Sensitive Quantitative Real-Time PCR for the Detection of Liver-Stage Parasite Burden following Low-Dose Sporozoite Challenge. PLoS One 8: e77811. doi: 10.1371/journal.pone.0077811
[71]
De Nova-Ocampo M, Villegas-Sepulveda N, del Angel RM (2002) Translation elongation factor-1alpha, La, and PTB interact with the 3′ untranslated region of dengue 4 virus RNA. Virology 295: 337–347. doi: 10.1006/viro.2002.1407
[72]
Chukkapalli V, Heaton NS, Randall G (2012) Lipids at the interface of virus-host interactions. Curr Opin Microbiol 15: 512–518. doi: 10.1016/j.mib.2012.05.013
[73]
Perera R, Riley C, Isaac G, Hopf-Jannasch AS, Moore RJ, et al. (2012) Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. PLoS Pathog 8: e1002584. doi: 10.1371/journal.ppat.1002584
[74]
Rothwell C, Lebreton A, Young Ng C, Lim JY, Liu W, et al.. (2009) Cholesterol biosynthesis modulation regulates dengue viral replication. Virology.
Altindis E (2013) Antibacterial Vaccine Research in 21st Century: From Inoculation to Genomics Approaches. Curr Top Med Chem.
[77]
Tanabe K, Zollner G, Vaughan JA, Sattabongkot J, Khuntirat B, et al.. (2013) Plasmodium falciparum: Genetic diversity and complexity of infections in an isolated village in western Thailand. Parasitol Int.
[78]
Bunyaratvej A, Butthep P, Yoksan S, Bhamarapravati N (1997) Dengue viruses induce cell proliferation and morphological changes of endothelial cells. Southeast Asian J Trop Med Public Health 28 Suppl 332–37.
[79]
Helt AM, Harris E (2005) S-phase-dependent enhancement of dengue virus 2 replication in mosquito cells, but not in human cells. J Virol 79: 13218–13230. doi: 10.1128/jvi.79.21.13218-13230.2005
[80]
Phoolcharoen W, Smith DR (2004) Internalization of the dengue virus is cell cycle modulated in HepG2, but not Vero cells. J Med Virol 74: 434–441. doi: 10.1002/jmv.20195
[81]
Davy C, Doorbar J (2007) G2/M cell cycle arrest in the life cycle of viruses. Virology 368: 219–226. doi: 10.1016/j.virol.2007.05.043
[82]
Kannan RP, Hensley LL, Evers LE, Lemon SM, McGivern DR (2011) Hepatitis C virus infection causes cell cycle arrest at the level of initiation of mitosis. J Virol 85: 7989–8001. doi: 10.1128/jvi.00280-11
[83]
Munday DC, Emmott E, Surtees R, Lardeau CH, Wu W, et al. (2010) Quantitative proteomic analysis of A549 cells infected with human respiratory syncytial virus. Mol Cell Proteomics 9: 2438–2459. doi: 10.1074/mcp.m110.001859
[84]
Hsing LC, Rudensky AY (2005) The lysosomal cysteine proteases in MHC class II antigen presentation. Immunol Rev 207: 229–241. doi: 10.1111/j.0105-2896.2005.00310.x
[85]
Reiser J, Adair B, Reinheckel T (2010) Specialized roles for cysteine cathepsins in health and disease. J Clin Invest 120: 3421–3431. doi: 10.1172/jci42918
[86]
Ducut Sigala JL, Bottero V, Young DB, Shevchenko A, Mercurio F, et al. (2004) Activation of transcription factor NF-kappaB requires ELKS, an IkappaB kinase regulatory subunit. Science 304: 1963–1967. doi: 10.1126/science.1098387
[87]
Grigoriev I, Splinter D, Keijzer N, Wulf PS, Demmers J, et al. (2007) Rab6 regulates transport and targeting of exocytotic carriers. Dev Cell 13: 305–314. doi: 10.1016/j.devcel.2007.06.010
[88]
Grigoriev I, Yu KL, Martinez-Sanchez E, Serra-Marques A, Smal I, et al. (2011) Rab6, Rab8, and MICAL3 cooperate in controlling docking and fusion of exocytotic carriers. Curr Biol 21: 967–974. doi: 10.1016/j.cub.2011.04.030
[89]
Stewart M (2007) Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol 8: 195–208. doi: 10.1038/nrm2114
[90]
Mason DA, Stage DE, Goldfarb DS (2009) Evolution of the metazoan-specific importin alpha gene family. J Mol Evol 68: 351–365. doi: 10.1007/s00239-009-9215-8
[91]
West AP, Shadel GS, Ghosh S (2011) Mitochondria in innate immune responses. Nat Rev Immunol 11: 389–402. doi: 10.1038/nri2975
[92]
Onoguchi K, Onomoto K, Takamatsu S, Jogi M, Takemura A, et al. (2010) Virus-infection or 5′ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1. PLoS Pathog 6: e1001012. doi: 10.1371/journal.ppat.1001012
[93]
Castanier C, Garcin D, Vazquez A, Arnoult D (2010) Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway. EMBO Rep 11: 133–138. doi: 10.1038/embor.2009.258
[94]
Schweneker M, Bachmann AS, Moelling K (2005) JM4 is a four-transmembrane protein binding to the CCR5 receptor. FEBS Lett 579: 1751–1758. doi: 10.1016/j.febslet.2005.02.037
[95]
Fo CS, Coleman CS, Wallick CJ, Vine AL, Bachmann AS (2006) Genomic organization, expression profile, and characterization of the new protein PRA1 domain family, member 2 (PRAF2). Gene 371: 154–165. doi: 10.1016/j.gene.2005.12.009
[96]
Vento MT, Zazzu V, Loffreda A, Cross JR, Downward J, et al. (2010) Praf2 is a novel Bcl-xL/Bcl-2 interacting protein with the ability to modulate survival of cancer cells. PLoS One 5: e15636. doi: 10.1371/journal.pone.0015636
Fehr AR, Yu D (2013) Control the Host Cell Cycle: Viral Regulation of the Anaphase-Promoting Complex. J Virol.
[99]
Arrington DD, Schnellmann RG (2008) Targeting of the molecular chaperone oxygen-regulated protein 150 (ORP150) to mitochondria and its induction by cellular stress. Am J Physiol Cell Physiol 294: C641–650. doi: 10.1152/ajpcell.00400.2007
[100]
Sanson M, Ingueneau C, Vindis C, Thiers JC, Glock Y, et al. (2008) Oxygen-regulated protein-150 prevents calcium homeostasis deregulation and apoptosis induced by oxidized LDL in vascular cells. Cell Death Differ 15: 1255–1265. doi: 10.1038/cdd.2008.36
