The Mediator CDK8-Cyclin C complex modulates Dpp signaling in Drosophila by stimulating Mad-dependent transcription
Autoři:
Xiao Li aff001; Mengmeng Liu aff001; Xingjie Ren aff002; Nicolas Loncle aff003; Qun Wang aff001; Rajitha-Udakara-Sampath Hemba-Waduge aff001; Stephen H. Yu aff001; Muriel Boube aff003; Henri-Marc G. Bourbon aff003; Jian-Quan Ni aff002; Jun-Yuan Ji aff001
Působiště autorů:
Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas, United States of America
aff001; School of Medicine, Tsinghua University, Beijing, China
aff002; Centre de Biologie Intégrative, Centre de Biologie du Développement, UMR5544 du CNRS, Université de Toulouse, Toulouse, France
aff003; Department of Nutrition, Texas A&M University, College Station, Texas, United States of America
aff004
Vyšlo v časopise:
The Mediator CDK8-Cyclin C complex modulates Dpp signaling in Drosophila by stimulating Mad-dependent transcription. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008832
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008832
Souhrn
Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C), two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. Thus, it is essential to understand the regulatory network modulating the CDK8-CycC complex in both normal development and tumorigenesis. To identify upstream regulators or downstream effectors of CDK8, we performed a dominant modifier genetic screen in Drosophila based on the defects in vein patterning caused by specific depletion or overexpression of CDK8 or CycC in developing wing imaginal discs. We identified 26 genomic loci whose haploinsufficiency can modify these CDK8- or CycC-specific phenotypes. Further analysis of two overlapping deficiency lines and mutant alleles led us to identify genetic interactions between the CDK8-CycC pair and the components of the Decapentaplegic (Dpp, the Drosophila homolog of TGFβ, or Transforming Growth Factor-β) signaling pathway. We observed that CDK8-CycC positively regulates transcription activated by Mad (Mothers against dpp), the primary transcription factor downstream of the Dpp/TGFβ signaling pathway. CDK8 can directly interact with Mad in vitro through the linker region between the DNA-binding MH1 (Mad homology 1) domain and the carboxy terminal MH2 (Mad homology 2) transactivation domain. Besides CDK8 and CycC, further analyses of other subunits of the MED complex have revealed six additional subunits that are required for Mad-dependent transcription in the wing discs: Med12, Med13, Med15, Med23, Med24, and Med31. Furthermore, our analyses confirmed the positive roles of CDK9 and Yorkie in regulating Mad-dependent gene expression in vivo. These results suggest that CDK8 and CycC, together with a few other subunits of the MED complex, may coordinate with other transcription cofactors in regulating Mad-dependent transcription during wing development in Drosophila.
Klíčová slova:
DPP signaling cascade – Drosophila melanogaster – Gene expression – Gene regulation – Phenotypes – Phosphorylation – Suppressor genes – Transcriptional control
Zdroje
1. Boube M, Joulia L, Cribbs DL, Bourbon HM (2002) Evidence for a mediator of RNA polymerase II transcriptional regulation conserved from yeast to man. Cell 110: 143–151. doi: 10.1016/s0092-8674(02)00830-9 12150923
2. Bourbon HM, Aguilera A, Ansari AZ, Asturias FJ, Berk AJ, et al. (2004) A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II. Mol Cell 14: 553–557. doi: 10.1016/j.molcel.2004.05.011 15175151
3. Kornberg RD (2005) Mediator and the mechanism of transcriptional activation. Trends Biochem Sci 30: 235–239. doi: 10.1016/j.tibs.2005.03.011 15896740
4. Soutourina J (2018) Transcription regulation by the Mediator complex. Nat Rev Mol Cell Biol 19: 262–274. doi: 10.1038/nrm.2017.115 29209056
5. Bourbon HM (2008) Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex. Nucleic Acids Res 36: 3993–4008. doi: 10.1093/nar/gkn349 18515835
6. Conaway RC, Conaway JW (2011) Function and regulation of the Mediator complex. Curr Opin Genet Dev 21: 225–230. doi: 10.1016/j.gde.2011.01.013 21330129
7. Fondell JD (2013) The Mediator complex in thyroid hormone receptor action. Biochim Biophys Acta 1830: 3867–3875. doi: 10.1016/j.bbagen.2012.02.012 22402254
8. Poss ZC, Ebmeier CC, Taatjes DJ (2013) The Mediator complex and transcription regulation. Crit Rev Biochem Mol Biol 48: 575–608. doi: 10.3109/10409238.2013.840259 24088064
9. Yin JW, Wang G (2014) The Mediator complex: a master coordinator of transcription and cell lineage development. Development 141: 977–987. doi: 10.1242/dev.098392 24550107
10. Morris EJ, Ji JY, Yang F, Di Stefano L, Herr A, et al. (2008) E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8. Nature 455: 552–556. doi: 10.1038/nature07310 18794899
11. Zhao J, Ramos R, Demma M (2013) CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation. Oncogene 32: 3520–3530. doi: 10.1038/onc.2012.364 22945643
12. Fryer CJ, White JB, Jones KA (2004) Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 16: 509–520. doi: 10.1016/j.molcel.2004.10.014 15546612
13. Donner AJ, Szostek S, Hoover JM, Espinosa JM (2007) CDK8 is a stimulus-specific positive coregulator of p53 target genes. Mol Cell 27: 121–133. doi: 10.1016/j.molcel.2007.05.026 17612495
14. Alarcon C, Zaromytidou AI, Xi Q, Gao S, Yu J, et al. (2009) Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell 139: 757–769. doi: 10.1016/j.cell.2009.09.035 19914168
15. Aleman A, Rios M, Juarez M, Lee D, Chen A, et al. (2014) Mad linker phosphorylations control the intensity and range of the BMP-activity gradient in developing Drosophila tissues. Sci Rep 4: 6927. doi: 10.1038/srep06927 25377173
16. Zhao X, Feng D, Wang Q, Abdulla A, Xie XJ, et al. (2012) Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1. J Clin Invest 122: 2417–2427. doi: 10.1172/JCI61462 22684109
17. Bancerek J, Poss ZC, Steinparzer I, Sedlyarov V, Pfaffenwimmer T, et al. (2013) CDK8 Kinase Phosphorylates Transcription Factor STAT1 to Selectively Regulate the Interferon Response. Immunity 38: 250–262. doi: 10.1016/j.immuni.2012.10.017 23352233
18. Clark AD, Oldenbroek M, Boyer TG (2015) Mediator kinase module and human tumorigenesis. Crit Rev Biochem Mol Biol 50: 393–426. doi: 10.3109/10409238.2015.1064854 26182352
19. Xu W, Ji JY (2011) Dysregulation of CDK8 and Cyclin C in tumorigenesis. J Genet Genomics 38: 439–452. doi: 10.1016/j.jgg.2011.09.002 22035865
20. Schiano C, Casamassimi A, Rienzo M, de Nigris F, Sommese L, et al. (2014) Involvement of Mediator complex in malignancy. Biochim Biophys Acta 1845: 66–83. doi: 10.1016/j.bbcan.2013.12.001 24342527
21. Spaeth JM, Kim NH, Boyer TG (2011) Mediator and human disease. Semin Cell Dev Biol 22: 776–787. doi: 10.1016/j.semcdb.2011.07.024 21840410
22. Li X, Liu M, Ji JY (2019) Understanding Obesity as a Risk Factor for Uterine Tumors Using Drosophila. Adv Exp Med Biol 1167: 129–155. doi: 10.1007/978-3-030-23629-8_8 31520353
23. Firestein R, Bass AJ, Kim SY, Dunn IF, Silver SJ, et al. (2008) CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature 455: 547–551. doi: 10.1038/nature07179 18794900
24. Kapoor A, Goldberg MS, Cumberland LK, Ratnakumar K, Segura MF, et al. (2010) The histone variant macroH2A suppresses melanoma progression through regulation of CDK8. Nature 468: 1105–1109. doi: 10.1038/nature09590 21179167
25. Broude EV, Gyorffy B, Chumanevich AA, Chen M, McDermott MS, et al. (2015) Expression of CDK8 and CDK8-interacting Genes as Potential Biomarkers in Breast Cancer. Curr Cancer Drug Targets 15: 739–749. doi: 10.2174/156800961508151001105814 26452386
26. Brewster CD, Birkenheuer CH, Vogt MB, Quackenbush SL, Rovnak J (2011) The retroviral cyclin of walleye dermal sarcoma virus binds cyclin-dependent kinases 3 and 8. Virology 409: 299–307. doi: 10.1016/j.virol.2010.10.022 21067790
27. Rovnak J, Quackenbush SL (2002) Walleye dermal sarcoma virus cyclin interacts with components of the mediator complex and the RNA polymerase II holoenzyme. J Virol 76: 8031–8039. doi: 10.1128/jvi.76.16.8031-8039.2002 12134008
28. Xu W, Wang Z, Zhang W, Qian K, Li H, et al. (2015) Mutated K-ras activates CDK8 to stimulate the epithelial-to-mesenchymal transition in pancreatic cancer in part via the Wnt/beta-catenin signaling pathway. Cancer Lett 356: 613–627. doi: 10.1016/j.canlet.2014.10.008 25305448
29. Osherovich L (2008) CDK8 is enough in colorectal cancer Science-Business eXchange 1: 5–7.
30. Rzymski T, Mikula M, Wiklik K, Brzozka K (2015) CDK8 kinase—An emerging target in targeted cancer therapy. Biochim Biophys Acta 1854: 1617–1629. doi: 10.1016/j.bbapap.2015.05.011 26006748
31. Aragon E, Goerner N, Zaromytidou AI, Xi Q, Escobedo A, et al. (2011) A Smad action turnover switch operated by WW domain readers of a phosphoserine code. Genes Dev 25: 1275–1288. doi: 10.1101/gad.2060811 21685363
32. Brand AH, Perrimon N (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401–415. 8223268
33. Duffy JB (2002) GAL4 system in Drosophila: a fly geneticist's Swiss army knife. Genesis 34: 1–15. doi: 10.1002/gene.10150 12324939
34. Kambadur R, Koizumi K, Stivers C, Nagle J, Poole SJ, et al. (1998) Regulation of POU genes by castor and hunchback establishes layered compartments in the Drosophila CNS. Genes Dev 12: 246–260. doi: 10.1101/gad.12.2.246 9436984
35. Milan M, Campuzano S, Garcia-Bellido A (1997) Developmental parameters of cell death in the wing disc of Drosophila. Proc Natl Acad Sci U S A 94: 5691–5696. doi: 10.1073/pnas.94.11.5691 9159134
36. Loncle N, Boube M, Joulia L, Boschiero C, Werner M, et al. (2007) Distinct roles for Mediator Cdk8 module subunits in Drosophila development. EMBO J 26: 1045–1054. doi: 10.1038/sj.emboj.7601566 17290221
37. Bridges CB (1919) Specific modifiers of eosin eye color in Drosophila melanogaster. J Exp Zool 28: 337–384.
38. St Johnston D (2002) The art and design of genetic screens: Drosophila melanogaster. Nat Rev Genet 3: 176–188. doi: 10.1038/nrg751 11972155
39. Ji JY, Haghnia M, Trusty C, Goldstein LS, Schubiger G (2002) A genetic screen for suppressors and enhancers of the Drosophila cdk1-cyclin B identifies maternal factors that regulate microtubule and microfilament stability. Genetics 162: 1179–1195. 12454065
40. Lee LA, Elfring LK, Bosco G, Orr-Weaver TL (2001) A genetic screen for suppressors and enhancers of the Drosophila PAN GU cell cycle kinase identifies cyclin B as a target. Genetics 158: 1545–1556. 11514446
41. Kennison JA, Tamkun JW (1988) Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. Proc Natl Acad Sci U S A 85: 8136–8140. doi: 10.1073/pnas.85.21.8136 3141923
42. Ji JY, Miles WO, Korenjak M, Zheng Y, Dyson NJ (2012) In vivo regulation of E2F1 by Polycomb group genes in Drosophila. G3 (Bethesda) 2: 1651–1660.
43. Nadeau JH (2003) Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 13: 290–295. doi: 10.1016/s0959-437x(03)00061-3 12787792
44. Nadeau JH (2001) Modifier genes in mice and humans. Nat Rev Genet 2: 165–174. doi: 10.1038/35056009 11256068
45. Parks AL, Cook KR, Belvin M, Dompe NA, Fawcett R, et al. (2004) Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nat Genet 36: 288–292. doi: 10.1038/ng1312 14981519
46. Cook RK, Christensen SJ, Deal JA, Coburn RA, Deal ME, et al. (2012) The generation of chromosomal deletions to provide extensive coverage and subdivision of the Drosophila melanogaster genome. Genome Biol 13: R21. doi: 10.1186/gb-2012-13-3-r21 22445104
47. Nagarkar-Jaiswal S, Lee PT, Campbell ME, Chen K, Anguiano-Zarate S, et al. (2015) A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila. Elife 4.
48. Tsuneizumi K, Nakayama T, Kamoshida Y, Kornberg TB, Christian JL, et al. (1997) Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature 389: 627–631. doi: 10.1038/39362 9335506
49. Hamaratoglu F, Affolter M, Pyrowolakis G (2014) Dpp/BMP signaling in flies: from molecules to biology. Semin Cell Dev Biol 32: 128–136. doi: 10.1016/j.semcdb.2014.04.036 24813173
50. Affolter M, Basler K (2007) The Decapentaplegic morphogen gradient: from pattern formation to growth regulation. Nat Rev Genet 8: 663–674. doi: 10.1038/nrg2166 17703237
51. Upadhyay A, Moss-Taylor L, Kim MJ, Ghosh AC, O'Connor MB (2017) TGF-beta Family Signaling in Drosophila. Cold Spring Harb Perspect Biol 9.
52. Massague J (2012) TGFbeta signalling in context. Nat Rev Mol Cell Biol 13: 616–630. doi: 10.1038/nrm3434 22992590
53. Raftery LA, Sutherland DJ (1999) TGF-beta family signal transduction in Drosophila development: from Mad to Smads. Dev Biol 210: 251–268. doi: 10.1006/dbio.1999.9282 10357889
54. Santibanez JF, Krstic J., Quintanilla M., Bernabeu C. (2016) TGF–β Signalling and Its Role in Cancer Progression and Metastasis. eLS.
55. Restrepo S, Zartman JJ, Basler K (2014) Coordination of patterning and growth by the morphogen DPP. Curr Biol 24: R245–255. doi: 10.1016/j.cub.2014.01.055 24650915
56. Affolter M, Marty T, Vigano MA, Jazwinska A (2001) Nuclear interpretation of Dpp signaling in Drosophila. EMBO J 20: 3298–3305. doi: 10.1093/emboj/20.13.3298 11432817
57. Moustakas A, Souchelnytskyi S, Heldin CH (2001) Smad regulation in TGF-beta signal transduction. J Cell Sci 114: 4359–4369. 11792802
58. Malik S, Roeder RG (2005) Dynamic regulation of pol II transcription by the mammalian Mediator complex. Trends Biochem Sci 30: 256–263. doi: 10.1016/j.tibs.2005.03.009 15896744
59. Blair SS (2007) Wing vein patterning in Drosophila and the analysis of intercellular signaling. Annu Rev Cell Dev Biol 23: 293–319. doi: 10.1146/annurev.cellbio.23.090506.123606 17506700
60. De Celis JF (2003) Pattern formation in the Drosophila wing: The development of the veins. Bioessays 25: 443–451. doi: 10.1002/bies.10258 12717815
61. de Celis JF, Barrio R (2000) Function of the spalt/spalt-related gene complex in positioning the veins in the Drosophila wing. Mech Dev 91: 31–41. doi: 10.1016/s0925-4773(99)00261-0 10704828
62. Crozatier M, Glise B, Vincent A (2004) Patterns in evolution: veins of the Drosophila wing. Trends Genet 20: 498–505. doi: 10.1016/j.tig.2004.07.013 15363904
63. Spradling AC, Stern D, Beaton A, Rhem EJ, Laverty T, et al. (1999) The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes. Genetics 153: 135–177. 10471706
64. Treisman JE, Rubin GM (1996) Targets of glass regulation in the Drosophila eye disc. Mech Dev 56: 17–24. doi: 10.1016/0925-4773(96)00508-4 8798144
65. Nellen D, Burke R, Struhl G, Basler K (1996) Direct and long-range action of a DPP morphogen gradient. Cell 85: 357–368. doi: 10.1016/s0092-8674(00)81114-9 8616891
66. Zecca M, Struhl G (2007) Control of Drosophila wing growth by the vestigial quadrant enhancer. Development 134: 3011–3020. doi: 10.1242/dev.006445 17634191
67. Zecca M, Struhl G (2007) Recruitment of cells into the Drosophila wing primordium by a feed-forward circuit of vestigial autoregulation. Development 134: 3001–3010. doi: 10.1242/dev.006411 17634192
68. Xu P, Lin X, Feng XH (2016) Posttranslational Regulation of Smads. Cold Spring Harb Perspect Biol 8.
69. Kato Y, Habas R, Katsuyama Y, Naar AM, He X (2002) A component of the ARC/Mediator complex required for TGF beta/Nodal signalling. Nature 418: 641–646. doi: 10.1038/nature00969 12167862
70. Terriente-Felix A, Lopez-Varea A, de Celis JF (2010) Identification of genes affecting wing patterning through a loss-of-function mutagenesis screen and characterization of med15 function during wing development. Genetics 185: 671–684. doi: 10.1534/genetics.109.113670 20233856
71. Fuentealba LC, Eivers E, Ikeda A, Hurtado C, Kuroda H, et al. (2007) Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell 131: 980–993. doi: 10.1016/j.cell.2007.09.027 18045539
72. Bacon CW, D'Orso I (2019) CDK9: a signaling hub for transcriptional control. Transcription 10: 57–75. doi: 10.1080/21541264.2018.1523668 30227759
73. Naar AM, Lemon BD, Tjian R (2001) Transcriptional coactivator complexes. Annu Rev Biochem 70: 475–501. doi: 10.1146/annurev.biochem.70.1.475 11395415
74. Allen BL, Taatjes DJ (2015) The Mediator complex: a central integrator of transcription. Nat Rev Mol Cell Biol 16: 155–166. doi: 10.1038/nrm3951 25693131
75. Stevens JL, Cantin GT, Wang G, Shevchenko A, Berk AJ (2002) Transcription control by E1A and MAP kinase pathway via Sur2 mediator subunit. Science 296: 755–758. doi: 10.1126/science.1068943 11934987
76. Galli GG, Carrara M, Yuan WC, Valdes-Quezada C, Gurung B, et al. (2015) YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers. Mol Cell 60: 328–337. doi: 10.1016/j.molcel.2015.09.001 26439301
77. Oh H, Slattery M, Ma L, Crofts A, White KP, et al. (2013) Genome-wide association of Yorkie with chromatin and chromatin-remodeling complexes. Cell Rep 3: 309–318. doi: 10.1016/j.celrep.2013.01.008 23395637
78. Tansey WP (2001) Transcriptional activation: risky business. Genes Dev 15: 1045–1050. doi: 10.1101/gad.896501 11331599
79. Cantelli G, Crosas-Molist E, Georgouli M, Sanz-Moreno V (2017) TGFBeta-induced transcription in cancer. Semin Cancer Biol 42: 60–69. doi: 10.1016/j.semcancer.2016.08.009 27586372
80. Kahata K, Dadras MS, Moustakas A (2018) TGF-beta Family Signaling in Epithelial Differentiation and Epithelial-Mesenchymal Transition. Cold Spring Harb Perspect Biol 10.
81. Yu Y, Feng XH (2019) TGF-beta signaling in cell fate control and cancer. Curr Opin Cell Biol 61: 56–63. doi: 10.1016/j.ceb.2019.07.007 31382143
82. Galbraith MD, Donner AJ, Espinosa JM (2010) CDK8: A positive regulator of transcription. Transcr 1: 4–12.
83. Eivers E, Fuentealba LC, Sander V, Clemens JC, Hartnett L, et al. (2009) Mad is required for wingless signaling in wing development and segment patterning in Drosophila. PLoS One 4: e6543. doi: 10.1371/journal.pone.0006543 19657393
84. Zhao M, Yang X, Fu Y, Wang H, Ning Y, et al. (2013) Mediator MED15 modulates transforming growth factor beta (TGFbeta)/Smad signaling and breast cancer cell metastasis. J Mol Cell Biol 5: 57–60. doi: 10.1093/jmcb/mjs054 23014762
85. de Celis JF, Barrio R (2009) Regulation and function of Spalt proteins during animal development. Int J Dev Biol 53: 1385–1398. doi: 10.1387/ijdb.072408jd 19247946
86. Organista MF, De Celis JF (2013) The Spalt transcription factors regulate cell proliferation, survival and epithelial integrity downstream of the Decapentaplegic signalling pathway. Biol Open 2: 37–48. doi: 10.1242/bio.20123038 23336075
87. Carrera I, Janody F, Leeds N, Duveau F, Treisman JE (2008) Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13. Proc Natl Acad Sci U S A 105: 6644–6649. doi: 10.1073/pnas.0709749105 18451032
88. Zhou H, Kim S, Ishii S, Boyer TG (2006) Mediator modulates Gli3-dependent Sonic hedgehog signaling. Mol Cell Biol 26: 8667–8682. doi: 10.1128/MCB.00443-06 17000779
89. Zhou H, Spaeth JM, Kim NH, Xu X, Friez MJ, et al. (2012) MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling. Proc Natl Acad Sci U S A 109: 19763–19768. doi: 10.1073/pnas.1121120109 23091001
90. Akoulitchev S, Chuikov S, Reinberg D (2000) TFIIH is negatively regulated by cdk8-containing mediator complexes. Nature 407: 102–106. doi: 10.1038/35024111 10993082
91. Ni JQ, Zhou R, Czech B, Liu LP, Holderbaum L, et al. (2011) A genome-scale shRNA resource for transgenic RNAi in Drosophila. Nat Methods 8: 405–407. doi: 10.1038/nmeth.1592 21460824
92. Qiao HH, Wang F, Xu RG, Sun J, Zhu R, et al. (2018) An efficient and multiple target transgenic RNAi technique with low toxicity in Drosophila. Nat Commun 9: 4160. doi: 10.1038/s41467-018-06537-y 30297884
93. Gobert V, Osman D, Bras S, Auge B, Boube M, et al. (2010) A genome-wide RNA interference screen identifies a differential role of the mediator CDK8 module subunits for GATA/ RUNX-activated transcription in drosophila. Mol Cell Biol 30: 2837–2848. doi: 10.1128/MCB.01625-09 20368357
94. Lahue EE, Smith AV, Orr-Weaver TL (1991) A novel cyclin gene from Drosophila complements CLN function in yeast. Genes Dev 5: 2166–2175. doi: 10.1101/gad.5.12a.2166 1836192
95. Xie XJ, Hsu FN, Gao X, Xu W, Ni JQ, et al. (2015) CDK8-Cyclin C Mediates Nutritional Regulation of Developmental Transitions through the Ecdysone Receptor in Drosophila. PLoS Biol 13: e1002207. doi: 10.1371/journal.pbio.1002207 26222308
96. Lu Q, Tang X, Tian G, Wang F, Liu K, et al. (2010) Arabidopsis homolog of the yeast TREX-2 mRNA export complex: components and anchoring nucleoporin. Plant J 61: 259–270. doi: 10.1111/j.1365-313X.2009.04048.x 19843313
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