{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T23:58:14Z","timestamp":1771372694515,"version":"3.50.1"},"reference-count":121,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,1,2]],"date-time":"2013-01-02T00:00:00Z","timestamp":1357084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Traffic"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:p><jats:bold>Nuclear translocation of proteins is an essential aspect of normal cell function, and defects in this process have been detected in many disease\u2010associated conditions. The detection and quantification of nuclear translocation was significantly boosted by the association of robotized microscopy with automated image analysis, a technology designated as high\u2010content screening. Image\u2010based high\u2010content screening and analysis provides the means to systematically observe cellular translocation events in time and space in response to chemical or genetic perturbation at large scale. This approach yields powerful insights into the regulation of complex signaling networks independently of preconceived notions of mechanistic relationships. In this review, we briefly overview the different mechanisms involved in nucleocytoplasmic protein trafficking. In addition, we discuss high\u2010content approaches used to interrogate the mechanistic and spatiotemporal dynamics of cellular signaling events using Forkhead box O (<jats:styled-content style=\"fixed-case\">FOXO<\/jats:styled-content>) proteins and the nuclear factor\u2010<jats:styled-content style=\"fixed-case\">\u03baB<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">NF\u2010\u03baB<\/jats:styled-content>) as important and clinically relevant examples.<\/jats:bold><\/jats:p><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tra12034-gra-0001.gif\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1111\/tra.12034","type":"journal-article","created":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T12:25:20Z","timestamp":1355401520000},"page":"247-258","source":"Crossref","is-referenced-by-count":35,"title":["Moving to the Core: Spatiotemporal Analysis of\u00a0Forkhead Box O (<scp>FOXO<\/scp>) and Nuclear Factor\u2010<scp>\u03baB<\/scp> (<scp>NF\u2010\u03baB<\/scp>) Nuclear Translocation"],"prefix":"10.1111","volume":"14","author":[{"given":"Fabian","family":"Zanella","sequence":"first","affiliation":[{"name":"School of Medicine, Cardiology Division University of California, San Diego  9500 Gilman Drive La Jolla CA 92093\u20100613 C USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuno R.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"IBB\u2010Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine (CBME) University of Algarve  de Gambelas, 8005\u2010139 Faro Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Link","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program, Departamento de Ci\u00eancias Biom\u00e9dicas e Medicina Universidade do Algarve  Faro Portugal"},{"name":"IBB\u2010Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine (CBME) University of Algarve  de Gambelas, 8005\u2010139 Faro Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,1,2]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.089110"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.12.004"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2928"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000562"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060109-151030"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.15.1.607"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.265"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2001-2-6-reviews3008"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.12.016"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2005.00268.x"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1274"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.108.000620"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1142204"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M909256199"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.03.003"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/311029a0"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0296-159"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0296-154"},{"key":"e_1_2_16_20_1","first-page":"1739","article-title":"Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia\u2010specific chromosome rearrangements","volume":"10","author":"Fornerod M","year":"1995","journal-title":"Oncogene"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.194"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203221"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986708786242859"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2145"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2008.07.004"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100141"},{"key":"e_1_2_16_27_1","first-page":"3","article-title":"Past, present, and future of high content screening and the field of cellomics","volume":"356","author":"Taylor DL","year":"2007","journal-title":"Methods Mol Biol"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2010.02.005"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(02)00313-7"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.11.025"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)14027-6"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth953"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-010-3657-0"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.013623"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2007.058"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057110374995"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2005.3.261"},{"key":"e_1_2_16_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057110384612"},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-384347"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00303-9"},{"key":"e_1_2_16_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.038984"},{"key":"e_1_2_16_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200800255"},{"key":"e_1_2_16_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.58"},{"key":"e_1_2_16_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-10-14"},{"key":"e_1_2_16_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803022105"},{"key":"e_1_2_16_46_1","doi-asserted-by":"publisher","DOI":"10.2174\/138620710790218249"},{"key":"e_1_2_16_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-007-0175-4"},{"key":"e_1_2_16_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2010.08.009"},{"key":"e_1_2_16_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)14023-9"},{"key":"e_1_2_16_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60327-258-2_8"},{"key":"e_1_2_16_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057106287136"},{"key":"e_1_2_16_52_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057104269989"},{"key":"e_1_2_16_53_1","doi-asserted-by":"publisher","DOI":"10.2174\/138620706777452447"},{"key":"e_1_2_16_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057108323910"},{"key":"e_1_2_16_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80595-4"},{"key":"e_1_2_16_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.21"},{"key":"e_1_2_16_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209086"},{"key":"e_1_2_16_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.029"},{"key":"e_1_2_16_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2223"},{"key":"e_1_2_16_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2664"},{"key":"e_1_2_16_61_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135931"},{"key":"e_1_2_16_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500528200"},{"key":"e_1_2_16_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094637"},{"key":"e_1_2_16_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600476"},{"key":"e_1_2_16_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.046"},{"key":"e_1_2_16_66_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.44.28897"},{"key":"e_1_2_16_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2012.09222.x"},{"key":"e_1_2_16_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.06.007"},{"key":"e_1_2_16_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.57"},{"key":"e_1_2_16_70_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-247361"},{"key":"e_1_2_16_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.09.012"},{"key":"e_1_2_16_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2772"},{"key":"e_1_2_16_73_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412357200"},{"key":"e_1_2_16_74_1","doi-asserted-by":"publisher","DOI":"10.1021\/np049624z"},{"key":"e_1_2_16_75_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0481"},{"key":"e_1_2_16_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1469"},{"key":"e_1_2_16_77_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-1059"},{"key":"e_1_2_16_78_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808890200"},{"key":"e_1_2_16_79_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802240200"},{"key":"e_1_2_16_80_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112475200"},{"key":"e_1_2_16_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00703-1"},{"key":"e_1_2_16_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.01.020"},{"key":"e_1_2_16_83_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132641"},{"key":"e_1_2_16_84_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1228704"},{"key":"e_1_2_16_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400234"},{"key":"e_1_2_16_86_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040196"},{"key":"e_1_2_16_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1464"},{"key":"e_1_2_16_88_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5488.2350"},{"key":"e_1_2_16_89_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1182364"},{"key":"e_1_2_16_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02794"},{"key":"e_1_2_16_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.177"},{"key":"e_1_2_16_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.033"},{"key":"e_1_2_16_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00423-5"},{"key":"e_1_2_16_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01648"},{"key":"e_1_2_16_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206761"},{"key":"e_1_2_16_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.07.030"},{"key":"e_1_2_16_97_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-11-21"},{"key":"e_1_2_16_98_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071914"},{"key":"e_1_2_16_99_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099962"},{"key":"e_1_2_16_100_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1680708"},{"key":"e_1_2_16_101_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600977"},{"key":"e_1_2_16_102_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112304"},{"key":"e_1_2_16_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2010.08.005"},{"key":"e_1_2_16_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2008.12.003"},{"key":"e_1_2_16_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09232"},{"key":"e_1_2_16_106_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164860"},{"key":"e_1_2_16_107_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09145"},{"key":"e_1_2_16_108_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3204"},{"key":"e_1_2_16_109_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.24.14255"},{"key":"e_1_2_16_110_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0958"},{"key":"e_1_2_16_111_1","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.4049\/jimmunol.161.11.6084","article-title":"Regulation of NF\u2010kappa B, AP\u20101, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF\u2010kappa B p50","volume":"161","author":"Torgerson TR","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_16_112_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0238"},{"key":"e_1_2_16_113_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21765"},{"key":"e_1_2_16_114_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002555"},{"key":"e_1_2_16_115_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057107301319"},{"key":"e_1_2_16_116_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(06)14009-4"},{"key":"e_1_2_16_117_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.582"},{"key":"e_1_2_16_118_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2011.171"},{"key":"e_1_2_16_119_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.026005"},{"key":"e_1_2_16_120_1","doi-asserted-by":"crossref","unstructured":"GrandaTG CebrianD MartinezS AnguitaPV LopezEC LinkW MerinoT PastorJ SereldeBG PeregrinaS PalaciosI AlbarranMI CebriaA LorenzoM AlonsoP et al. Biological characterization of ETP\u201046321 a selective and efficacious inhibitor of phosphoinositide\u20103\u2010kinases. Investigational New Drugs May2012 DOI 10.1007\/s10637-012-9835-5.","DOI":"10.1007\/s10637-012-9835-5"},{"key":"e_1_2_16_121_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.03.090"},{"key":"e_1_2_16_122_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01608.x"}],"container-title":["Traffic"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ftra.12034","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tra.12034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T20:04:38Z","timestamp":1698523478000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/tra.12034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,2]]},"references-count":121,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1111\/tra.12034"],"URL":"https:\/\/doi.org\/10.1111\/tra.12034","archive":["Portico"],"relation":{},"ISSN":["1398-9219","1600-0854"],"issn-type":[{"value":"1398-9219","type":"print"},{"value":"1600-0854","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,2]]}}}