Control of Multicellular Development by the Physically Interacting Deneddylases DEN1/DenA and COP9 Signalosome

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Deneddylases remove the ubiquitin-like protein Nedd8 from modified proteins. An increased deneddylase activity has been associated with various human cancers. In contrast, we show here that a mutant strain of the model fungus Aspergillus nidulans deficient in two deneddylases is viable but can only grow as a filament and is highly impaired for multicellular development. The DEN1/DenA and the COP9 signalosome (CSN) deneddylases physically interact in A. nidulans as well as in human cells, and CSN targets DEN1/DenA for protein degradation. Fungal development responds to light and requires both deneddylases for an appropriate light reaction. In contrast to CSN, which is necessary for sexual development, DEN1/DenA is required for asexual development. The CSN-DEN1/DenA interaction that affects DEN1/DenA protein levels presumably balances cellular deneddylase activity. A deneddylase disequilibrium impairs multicellular development and suggests that control of deneddylase activity is important for multicellular development.

Vyšlo v časopise: Control of Multicellular Development by the Physically Interacting Deneddylases DEN1/DenA and COP9 Signalosome. PLoS Genet 9(2): e32767. doi:10.1371/journal.pgen.1003275
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003275

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Zdroje

1. KerscherO, FelberbaumR, HochstrasserM (2006) Modification of Proteins by Ubiquitin and Ubiquitin-Like Proteins. Annual Review of Cell and Developmental Biology

2. HershkoA, CiechanoverA (1998) The ubiquitin system. Annu Rev Biochem 67 : 425–479.

3. PetroskiMD, DeshaiesRJ (2005) Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 6 : 9–20.

4. von Zeska Kress MR, Harting R, Bayram O, Christmann M, Irmer H, et al.. (2012) The COP9 signalosome prevents the accumulation of cullin SCF ubiquitin E3 RING ligases during fungal development. Mol Microbiol, accepted for publication.

5. MorimotoM, NishidaT, NagayamaY, YasudaH (2003) Nedd8-modification of Cul1 is promoted by Roc1 as a Nedd8-E3 ligase and regulates its stability. Biochemical and Biophysical Research Communications 301 : 392–398.

6. DudaDM, BorgLA, ScottDC, HuntHW, HammelM, et al. (2008) Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell 134 : 995–1006.

7. WatsonIR, IrwinMS, OhhM (2011) NEDD8 pathways in cancer, Sine Quibus Non. Cancer Cell 19 : 168–176.

8. LiuJ, FurukawaM, MatsumotoT, XiongY (2002) NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases. Mol Cell 10 : 1511–1518.

9. HelmstaedtK, SchwierEU, ChristmannM, NahlikK, WestermannM, et al. (2011) Recruitment of the inhibitor Cand1 to the cullin substrate adaptor site mediates interaction to the neddylation site. Mol Biol Cell 22 : 153–164.

10. SchmidtMW, McQuaryPR, WeeS, HofmannK, WolfDA (2009) F-box-directed CRL complex assembly and regulation by the CSN and CAND1. Mol Cell 35 : 586–597.

11. Schmaler T, Dubiel W (2010) Control of deneddylation by the COP9 signalosome; Groettrup M, editor. Austin, New York: Landes Bioscience and Springer Science+Business Media. 57–68 p.

12. ReverterD, WuK, ErdeneTG, PanZQ, WilkinsonKD, et al. (2005) Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1. Journal of Molecular Biology 345 : 141–151.

13. WadaH, KitoK, CaskeyLS, YehET, KamitaniT (1998) Cleavage of the C-terminus of NEDD8 by UCH-L3. Biochemical and Biophysical Research Communications 251 : 688–692.

14. BuschS, SchwierEU, NahlikK, BayramO, HelmstaedtK, et al. (2007) An eight-subunit COP9 signalosome with an intact JAMM motif is required for fungal fruit body formation. Proceedings of the National Academy of Sciences of the United States of America 104 : 8089–8094.

15. KatoJY, Yoneda-KatoN (2009) Mammalian COP9 signalosome. Genes to Cells 14 : 1209–1225.

16. CopeGA, SuhGS, AravindL, SchwarzSE, ZipurskySL, et al. (2002) Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1. Science 298 : 608–611.

17. DeshaiesRJ, JoazeiroCA (2009) RING domain E3 ubiquitin ligases. Annual Review of Biochemistry 78 : 399–434.

18. HuangX, HetfeldBK, SeifertU, KahneT, KloetzelPM, et al. (2005) Consequences of COP9 signalosome and 26S proteasome interaction. Febs J 272 : 3909–3917.

19. EnchevRI, ScottDC, da FonsecaPC, SchreiberA, MondaJK, et al. (2012) Structural Basis for a Reciprocal Regulation between SCF and CSN. Cell Rep 2 : 616–627.

20. UhleS, MedaliaO, WaldronR, DumdeyR, HenkleinP, et al. (2003) Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. EMBO Journal 22 : 1302–1312.

21. HetfeldBK, HelfrichA, KapelariB, ScheelH, HofmannK, et al. (2005) The zinc finger of the CSN-associated deubiquitinating enzyme USP15 is essential to rescue the E3 ligase Rbx1. Current Biology 15 : 1217–1221.

22. HuangX, LangelotzC, Hetfeld-PechocBK, SchwenkW, DubielW (2009) The COP9 signalosome mediates beta-catenin degradation by deneddylation and blocks adenomatous polyposis coli destruction via USP15. Journal of Molecular Biology 391 : 691–702.

23. SchwechheimerC, SerinoG, CallisJ, CrosbyWL, LyapinaS, et al. (2001) Interactions of the COP9 signalosome with the E3 ubiquitin ligase SCFTIRI in mediating auxin response. Science 292 : 1379–1382.

24. WolfDA, ZhouC, WeeS (2003) The COP9 signalosome: an assembly and maintenance platform for cullin ubiquitin ligases? Nat Cell Biol 5 : 1029–1033.

25. BrausGH, IrnigerS, BayramO (2010) Fungal development and the COP9 signalosome. Curr Opin Microbiol 13 : 672–676.

26. KnowlesA, KohK, WuJT, ChienCT, ChamovitzDA, et al. (2009) The COP9 signalosome is required for light-dependent timeless degradation and Drosophila clock resetting. J Neurosci 29 : 1152–1162.

27. ZhouZ, WangY, CaiG, HeQ (2012) Neurospora COP9 signalosome integrity plays major roles for hyphal growth, conidial development, and circadian function. PLoS Genet 8: e1002712 doi:10.1371/journal.ppat.1002712.

28. WeiN, DengXW (1999) Making sense of the COP9 signalosome. A regulatory protein complex conserved from Arabidopsis to human. Trends Genet 15 : 98–103.

29. FreilichS, OronE, KappY, Nevo-CaspiY, OrgadS, et al. (1999) The COP9 signalosome is essential for development of Drosophila melanogaster. Current Biology 9 : 1187–1190.

30. FukumotoA, IkedaN, ShoM, TomodaK, KanehiroH, et al. (2004) Prognostic significance of localized p27Kip1 and potential role of Jab1/CSN5 in pancreatic cancer. Oncology Reports 11 : 277–284.

31. Gan-ErdeneT, NagamalleswariK, YinL, WuK, PanZQ, et al. (2003) Identification and characterization of DEN1, a deneddylase of the ULP family. Journal of Biological Chemistry 278 : 28892–28900.

32. ShenLN, LiuH, DongC, XirodimasD, NaismithJH, et al. (2005) Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1. EMBO Journal 24 : 1341–1351.

33. WuK, YamoahK, DoliosG, Gan-ErdeneT, TanP, et al. (2003) DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1. Journal of Biological Chemistry 278 : 28882–28891.

34. ZhouL, WattsFZ (2005) Nep1, a Schizosaccharomyces pombe deneddylating enzyme. Biochemical Journal 389 : 307–314.

35. ChanY, YoonJ, WuJT, KimHJ, PanKT, et al. (2008) DEN1 deneddylates non-cullin proteins in vivo. Journal of Cell Science 121 : 3218–3223.

36. WatsonIR, LiBK, RocheO, BlanchA, OhhM, et al. (2010) Chemotherapy induces NEDP1-mediated destabilization of MDM2. Oncogene 29 : 297–304.

37. BroemerM, TenevT, RigboltKT, HempelS, BlagoevB, et al. (2010) Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases. Molecular Cell 40 : 810–822.

38. AxelrodDE, GealtM, PastushokM (1973) Gene control of developmental competence in Aspergillus nidulans. Dev Biol 34 : 9–15.

39. BayramO, BrausGH (2011) Coordination of secondary metabolism and development in fungi: the velvet family of regulatory proteins. FEMS Microbiol Rev

40. GalaganJE, CalvoSE, CuomoC, MaLJ, WortmanJR, et al. (2005) Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438 : 1105–1115.

41. FrohmanMA, DushMK, MartinGR (1988) Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proceedings of the National Academy of Sciences of the United States of America 85 : 8998–9002.

42. BayramO, BrausGH, FischerR, Rodriguez-RomeroJ (2010) Spotlight on Aspergillus nidulans photosensory systems. Fungal Genet Biol 47 : 900–908.

43. MendozaHM, ShenLN, BottingC, LewisA, ChenJ, et al. (2003) NEDP1, a highly conserved cysteine protease that deNEDDylates Cullins. Journal of Biological Chemistry 278 : 25637–25643.

44. LinghuB, CallisJ, GoeblMG (2002) Rub1p processing by Yuh1p is required for wild-type levels of Rub1p conjugation to Cdc53p. Eukaryot Cell 1 : 491–494.

45. BuschS, EckertSE, KrappmannS, BrausGH (2003) The COP9 signalosome is an essential regulator of development in the filamentous fungus Aspergillus nidulans. Molecular Microbiology 49 : 717–730.

46. NahlikK, DumkowM, BayramO, HelmstaedtK, BuschS, et al. (2010) The COP9 signalosome mediates transcriptional and metabolic response to hormones, oxidative stress protection and cell wall rearrangement during fungal development. Mol Microbiol 78 : 964–979.

47. TomodaK, KubotaY, ArataY, MoriS, MaedaM, et al. (2002) The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. Journal of Biological Chemistry 277 : 2302–2310.

48. PethA, BerndtC, HenkeW, DubielW (2007) Downregulation of COP9 signalosome subunits differentially affects the CSN complex and target protein stability. BMC Biochem 8 : 27.

49. LeppertU, HenkeW, HuangX, MullerJM, DubielW (2011) Post-transcriptional fine-tuning of COP9 signalosome subunit biosynthesis is regulated by the c-Myc/Lin28B/let-7 pathway. J Mol Biol 409 : 710–721.

50. Bech-OtschirD, KraftR, HuangX, HenkleinP, KapelariB, et al. (2001) COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO Journal 20 : 1630–1639.

51. HuangX, WagnerE, DumdeyR, PethA, BerseM, et al. (2006) Phosphorylation by COP9 signalosome-associated CK2 promotes degradation of p27 during the G1 cell cycle phase. Israel Journal of Chemistry 46 : 231–238.

52. ZhengJ, YangX, HarrellJM, RyzhikovS, ShimEH, et al. (2002) CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Mol Cell 10 : 1519–1526.

53. HwangJW, MinKW, TamuraTA, YoonJB (2003) TIP120A associates with unneddylated cullin 1 and regulates its neddylation. FEBS Lett 541 : 102–108.

54. WuJT, LinHC, HuYC, ChienCT (2005) Neddylation and deneddylation regulate Cul1 and Cul3 protein accumulation. Nat Cell Biol 7 : 1014–1020.

55. MukhopadhyayD, DassoM (2007) Modification in reverse: the SUMO proteases. Trends Biochem Sci 32 : 286–295.

56. Bennet JW, Lasure LL (1991) Growth media. In: Bennet JW, Lasure LL, editors. More Gene Manipulation in Fungi. San Diego: Academic Press Inc. pp. 441–457.

57. KäferE (1977) Meiotic and mitotic recombination in Aspergillus and its chromosomal aberrations. Adv Genet 19 : 33–131.

58. Clutterbuck AJ (1974) Aspergillus nidulans. In: King RC, editor. Handbook of Genetics. New York: Plenum. pp. 447–510.

59. InoueH, NojimaH, OkayamaH (1990) High efficiency transformation of Escherichia coli with plasmids. Gene 96 : 23–28.

60. EckertSE, KublerE, HoffmannB, BrausGH (2000) The tryptophan synthase-encoding trpB gene of Aspergillus nidulans is regulated by the cross-pathway control system. Mol Gen Genet 263 : 867–876.

61. Lee BS, Taylor JW (1990) Isolation of DNA from fungal mycelia and single spores. In: Innis MA, Gelfand DH, Sninsky JS, White TJ, editors. PCR Protocols: a Guide to Methods and Applications. San Diego: Academic Press Inc. pp. 282–287.

62. RaveN, CrkvenjakovR, BoedtkerH (1979) Identification of procollagen mRNAs transferred to diazobenzyloxymethyl paper from formaldehyde agarose gels. Nucleic Acids Res 6 : 3559–3567.

63. BussinkHJ, OsmaniSA (1998) A cyclin-dependent kinase family member (PHOA) is required to link developmental fate to environmental conditions in Aspergillus nidulans. EMBO J 17 : 3990–4003.

64. Streckfuss-BomekeK, SchulzeF, HerzogB, ScholzE, BrausGH (2009) Degradation of Saccharomyces cerevisiae transcription factor Gcn4 requires a C-terminal nuclear localization signal in the cyclin Pcl5. Eukaryot Cell 8 : 496–510.

65. TesfaigziJ, Smith-HarrisonW, CarlsonDM (1994) A simple method for reusing western blots on PVDF membranes. Biotechniques 17 : 268–269.

66. KapelariB, Bech-OtschirD, HegerlR, SchadeR, DumdeyR, et al. (2000) Electron microscopy and subunit-subunit interaction studies reveal a first architecture of COP9 signalosome. Journal of Molecular Biology 300 : 1169–1178.

67. LiT, PavletichNP, SchulmanBA, ZhengN (2005) High-level expression and purification of recombinant SCF ubiquitin ligases. Methods Enzymol 398 : 125–142.

68. Golemis E, Serebriiskii I, Finley RJ, Kolonin M, Gyuris J, et al.. (1999) Interaction trap/two-hybrid system to identify interacting proteins. In: Ausubel FM, Brent R, Kingston RE, Moore DD, Seidmann JG et al.., editors. Current protocols in molecular biology. New York: John Wiley & Sons, Inc. pp. 20.21.21–20.21.40.

69. HelmstaedtK, LaubingerK, VosskuhlK, BayramO, BuschS, et al. (2008) The nuclear migration protein NUDF/LIS1 forms a complex with NUDC and BNFA at spindle pole bodies. Eukaryot Cell 7 : 1041–1052.

70. JiangR, CarlsonM (1997) The Snf1 protein kinase and its activating subunit, Snf4, interact with distinct domains of the Sip1/Sip2/Gal83 component in the kinase complex. Mol Cell Biol 17 : 2099–2106.

71. NayakT, SzewczykE, OakleyCE, OsmaniA, UkilL, et al. (2006) A versatile and efficient gene-targeting system for Aspergillus nidulans. Genetics 172 : 1557–1566.