Cyclin B3 activates the Anaphase-Promoting Complex/Cyclosome in meiosis and mitosis

English version

Autoři: Damien Garrido ^aff001; Mohammed Bourouh ^aff001; Éric Bonneil ^aff001; Pierre Thibault ^aff001; Andrew Swan ^aff003; Vincent Archambault ^aff001
Působiště autorů: Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Canada ^aff001; Département de biochimie et médecine moléculaire, Université de Montréal, Montreal, Canada ^aff002; Department of Biomedical Sciences, University of Windsor, Montreal, Canada ^aff003; Département de chimie, Université de Montréal, Montreal, Canada ^aff004
Vyšlo v časopise: Cyclin B3 activates the Anaphase-Promoting Complex/Cyclosome in meiosis and mitosis. PLoS Genet 16(11): e32767. doi:10.1371/journal.pgen.1009184
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009184

Souhrn

In mitosis and meiosis, chromosome segregation is triggered by the Anaphase-Promoting Complex/Cyclosome (APC/C), a multi-subunit ubiquitin ligase that targets proteins for degradation, leading to the separation of chromatids. APC/C activation requires phosphorylation of its APC3 and APC1 subunits, which allows the APC/C to bind its co-activator Cdc20. The identity of the kinase(s) responsible for APC/C activation in vivo is unclear. Cyclin B3 (CycB3) is an activator of the Cyclin-Dependent Kinase 1 (Cdk1) that is required for meiotic anaphase in flies, worms and vertebrates. It has been hypothesized that CycB3-Cdk1 may be responsible for APC/C activation in meiosis but this remains to be determined. Using Drosophila, we found that mutations in CycB3 genetically enhance mutations in tws, which encodes the B55 regulatory subunit of Protein Phosphatase 2A (PP2A) known to promote mitotic exit. Females heterozygous for CycB3 and tws loss-of-function alleles lay embryos that arrest in mitotic metaphase in a maternal effect, indicating that CycB3 promotes anaphase in mitosis in addition to meiosis. This metaphase arrest is not due to the Spindle Assembly Checkpoint (SAC) because mutation of mad2 that inactivates the SAC does not rescue the development of embryos from CycB3^-/+, tws^-/+ females. Moreover, we found that CycB3 promotes APC/C activity and anaphase in cells in culture. We show that CycB3 physically associates with the APC/C, is required for phosphorylation of APC3, and promotes APC/C association with its Cdc20 co-activators Fizzy and Cortex. Our results strongly suggest that CycB3-Cdk1 directly activates the APC/C to promote anaphase in both meiosis and mitosis.

Klíčová slova:

Anaphase – Cyclins – Drosophila melanogaster – Meiosis – Metaphase – Mitosis – Phosphorylation – Eggs

Zdroje

1. Morgan DO. The Cell Cycle: Principles of Control. London: New Science Press; 2007. 297 p.

2. Holder J, Poser E, Barr FA. Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A. FEBS Lett. 2019;593(20):2908–24. doi: 10.1002/1873-3468.13595 31494926

3. Schellhaus AK, De Magistris P, Antonin W. Nuclear Reformation at the End of Mitosis. J Mol Biol. 2016;428(10 Pt A):1962–85. doi: 10.1016/j.jmb.2015.09.016 26423234

4. Yamano H. APC/C: current understanding and future perspectives. F1000Res. 2019;8. doi: 10.12688/f1000research.18582.1 31164978

5. Alfieri C, Zhang S, Barford D. Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C). Open Biol. 2017;7(11).

6. King RW, Peters JM, Tugendreich S, Rolfe M, Hieter P, Kirschner MW. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell. 1995;81(2):279–88. doi: 10.1016/0092-8674(95)90338-0 7736580

7. Sudakin V, Ganoth D, Dahan A, Heller H, Hershko J, Luca FC, et al. The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol Biol Cell. 1995;6(2):185–97. doi: 10.1091/mbc.6.2.185 7787245

8. Funabiki H, Yamano H, Kumada K, Nagao K, Hunt T, Yanagida M. Cut2 proteolysis required for sister-chromatid seperation in fission yeast. Nature. 1996;381(6581):438–41. doi: 10.1038/381438a0 8632802

9. Cohen-Fix O, Peters JM, Kirschner MW, Koshland D. Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p. Genes Dev. 1996;10(24):3081–93. doi: 10.1101/gad.10.24.3081 8985178

10. Ciosk R, Zachariae W, Michaelis C, Shevchenko A, Mann M, Nasmyth K. An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast. Cell. 1998;93(6):1067–76. doi: 10.1016/s0092-8674(00)81211-8 9635435

11. Uhlmann F, Lottspeich F, Nasmyth K. Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1. Nature. 1999;400(6739):37–42. doi: 10.1038/21831 10403247

12. Visintin R, Prinz S, Amon A. CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science. 1997;278(5337):460–3. doi: 10.1126/science.278.5337.460 9334304

13. Fang G, Yu H, Kirschner MW. Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. Mol Cell. 1998;2(2):163–71. doi: 10.1016/s1097-2765(00)80126-4 9734353

14. Corbett KD. Molecular Mechanisms of Spindle Assembly Checkpoint Activation and Silencing. Prog Mol Subcell Biol. 2017;56:429–55. doi: 10.1007/978-3-319-58592-5_18 28840248

15. Labit H, Fujimitsu K, Bayin NS, Takaki T, Gannon J, Yamano H. Dephosphorylation of Cdc20 is required for its C-box-dependent activation of the APC/C. EMBO J. 2012;31(15):3351–62. doi: 10.1038/emboj.2012.168 22713866

16. Fujimitsu K, Yamano H. PP2A-B56 binds to Apc1 and promotes Cdc20 association with the APC/C ubiquitin ligase in mitosis. EMBO Rep. 2020;21(1):e48503. doi: 10.15252/embr.201948503 31825153

17. Hein JB, Hertz EPT, Garvanska DH, Kruse T, Nilsson J. Distinct kinetics of serine and threonine dephosphorylation are essential for mitosis. Nat Cell Biol. 2017;19(12):1433–40. doi: 10.1038/ncb3634 29084198

18. Kramer ER, Scheuringer N, Podtelejnikov AV, Mann M, Peters JM. Mitotic regulation of the APC activator proteins CDC20 and CDH1. Mol Biol Cell. 2000;11(5):1555–69. doi: 10.1091/mbc.11.5.1555 10793135

19. Zhang S, Chang L, Alfieri C, Zhang Z, Yang J, Maslen S, et al. Molecular mechanism of APC/C activation by mitotic phosphorylation. Nature. 2016;533(7602):260–4. doi: 10.1038/nature17973 27120157

20. Fujimitsu K, Grimaldi M, Yamano H. Cyclin-dependent kinase 1-dependent activation of APC/C ubiquitin ligase. Science. 2016;352(6289):1121–4. doi: 10.1126/science.aad3925 27103671

21. Fung TK, Poon RY. A roller coaster ride with the mitotic cyclins. Semin Cell Dev Biol. 2005;16(3):335–42. doi: 10.1016/j.semcdb.2005.02.014 15840442

22. Li J, Qian WP, Sun QY. Cyclins regulating oocyte meiotic cell cycle progressiondagger. Biol Reprod. 2019;101(5):878–81. doi: 10.1093/biolre/ioz143 31347666

23. Hein JB, Nilsson J. Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry. Nat Commun. 2016;7:10975. doi: 10.1038/ncomms10975 26960431

24. Lindqvist A, Rodriguez-Bravo V, Medema RH. The decision to enter mitosis: feedback and redundancy in the mitotic entry network. J Cell Biol. 2009;185(2):193–202. doi: 10.1083/jcb.200812045 19364923

25. Zhang Y, Zhu CC, Sun SC. Cyclin B3: an anaphase onset controller in meiosis. Cell Cycle. 2015;14(19):3013. doi: 10.1080/15384101.2015.1084201 26496167

26. Gallant P, Nigg EA. Identification of a novel vertebrate cyclin: cyclin B3 shares properties with both A- and B-type cyclins. EMBO J. 1994;13(3):595–605. 8313904

27. McCleland ML, Farrell JA, O’Farrell PH. Influence of cyclin type and dose on mitotic entry and progression in the early Drosophila embryo. J Cell Biol. 2009;184(5):639–46. doi: 10.1083/jcb.200810012 19273612

28. Yuan K, O’Farrell PH. Cyclin B3 is a mitotic cyclin that promotes the metaphase-anaphase transition. Curr Biol. 2015;25(6):811–6. doi: 10.1016/j.cub.2015.01.053 25754637

29. Lehner CF, O’Farrell PH. Expression and function of Drosophila cyclin A during embryonic cell cycle progression. Cell. 1989;56(6):957–68. doi: 10.1016/0092-8674(89)90629-6 2564316

30. Reber A, Lehner CF, Jacobs HW. Terminal mitoses require negative regulation of Fzr/Cdh1 by Cyclin A, preventing premature degradation of mitotic cyclins and String/Cdc25. Development. 2006;133(16):3201–11. doi: 10.1242/dev.02488 16854973

31. Jacobs HW, Knoblich JA, Lehner CF. Drosophila Cyclin B3 is required for female fertility and is dispensable for mitosis like Cyclin B. Genes Dev. 1998;12(23):3741–51. doi: 10.1101/gad.12.23.3741 9851980

32. Bourouh M, Dhaliwal R, Rana K, Sinha S, Guo Z, Swan A. Distinct and Overlapping Requirements for Cyclins A, B, and B3 in Drosophila Female Meiosis. G3 (Bethesda). 2016;6(11):3711–24.

33. Zhang T, Qi ST, Huang L, Ma XS, Ouyang YC, Hou Y, et al. Cyclin B3 controls anaphase onset independent of spindle assembly checkpoint in meiotic oocytes. Cell Cycle. 2015;14(16):2648–54. doi: 10.1080/15384101.2015.1064567 26125114

34. Karasu ME, Bouftas N, Keeney S, Wassmann K. Cyclin B3 promotes anaphase I onset in oocyte meiosis. J Cell Biol. 2019;218(4):1265–81. doi: 10.1083/jcb.201808091 30723090

35. Li Y, Wang L, Zhang L, He Z, Feng G, Sun H, et al. Cyclin B3 is required for metaphase to anaphase transition in oocyte meiosis I. J Cell Biol. 2019;218(5):1553–63. doi: 10.1083/jcb.201808088 30770433

36. Deyter GM, Furuta T, Kurasawa Y, Schumacher JM. Caenorhabditis elegans cyclin B3 is required for multiple mitotic processes including alleviation of a spindle checkpoint-dependent block in anaphase chromosome segregation. PLoS Genet. 2010;6(11):e1001218. doi: 10.1371/journal.pgen.1001218 21124864

37. Mehsen H, Boudreau V, Garrido D, Bourouh M, Larouche M, Maddox PS, et al. PP2A-B55 promotes nuclear envelope reformation after mitosis in Drosophila. J Cell Biol. 2018;217(12):4106–23. doi: 10.1083/jcb.201804018 30309980

38. Mayer-Jaekel RE, Ohkura H, Ferrigno P, Andjelkovic N, Shiomi K, Uemura T, et al. Drosophila mutants in the 55 kDa regulatory subunit of protein phosphatase 2A show strongly reduced ability to dephosphorylate substrates of p34cdc2. J Cell Sci. 1994;107 (Pt 9):2609–16. 7844174

39. Li D, Morley G, Whitaker M, Huang JY. Recruitment of Cdc20 to the kinetochore requires BubR1 but not Mad2 in Drosophila melanogaster. Mol Cell Biol. 2010;30(13):3384–95. doi: 10.1128/MCB.00258-10 20421417

40. Swan A, Schupbach T. The Cdc20 (Fzy)/Cdh1-related protein, Cort, cooperates with Fzy in cyclin destruction and anaphase progression in meiosis I and II in Drosophila. Development. 2007;134(5):891–9. doi: 10.1242/dev.02784 17251266

41. Dawson IA, Roth S, Artavanis-Tsakonas S. The Drosophila cell cycle gene fizzy is required for normal degradation of cyclins A and B during mitosis and has homology to the CDC20 gene of Saccharomyces cerevisiae. J Cell Biol. 1995;129(3):725–37. doi: 10.1083/jcb.129.3.725 7730407

42. Pesin JA, Orr-Weaver TL. Developmental role and regulation of cortex, a meiosis-specific anaphase-promoting complex/cyclosome activator. PLoS Genet. 2007;3(11):e202. doi: 10.1371/journal.pgen.0030202 18020708

43. Knoblich JA, Lehner CF. Synergistic action of Drosophila cyclins A and B during the G2-M transition. EMBO J. 1993;12(1):65–74. 8428595

44. Wang Z, Lin H. The division of Drosophila germline stem cells and their precursors requires a specific cyclin. Curr Biol. 2005;15(4):328–33. doi: 10.1016/j.cub.2005.02.016 15723793

45. Echard A, O’Farrell PH. The degradation of two mitotic cyclins contributes to the timing of cytokinesis. Curr Biol. 2003;13(5):373–83. doi: 10.1016/s0960-9822(03)00127-1 12620185

46. Huang JY, Raff JW. The dynamic localisation of the Drosophila APC/C: evidence for the existence of multiple complexes that perform distinct functions and are differentially localised. J Cell Sci. 2002;115(Pt 14):2847–56. 12082146

47. Hegemann B, Hutchins JR, Hudecz O, Novatchkova M, Rameseder J, Sykora MM, et al. Systematic phosphorylation analysis of human mitotic protein complexes. Sci Signal. 2011;4(198):rs12. doi: 10.1126/scisignal.2001993 22067460

48. Sigrist S, Jacobs H, Stratmann R, Lehner CF. Exit from mitosis is regulated by Drosophila fizzy and the sequential destruction of cyclins A, B and B3. EMBO J. 1995;14(19):4827–38. 7588612

49. Raff JW, Jeffers K, Huang JY. The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of cyclin B in space and time. J Cell Biol. 2002;157(7):1139–49. doi: 10.1083/jcb.200203035 12082076

50. Patra D, Dunphy WG. Xe-p9, a Xenopus Suc1/Cks protein, is essential for the Cdc2-dependent phosphorylation of the anaphase- promoting complex at mitosis. Genes Dev. 1998;12(16):2549–59. doi: 10.1101/gad.12.16.2549 9716407

51. Shteinberg M, Hershko A. Role of Suc1 in the activation of the cyclosome by protein kinase Cdk1/cyclin B. Biochem Biophys Res Commun. 1999;257(1):12–8. doi: 10.1006/bbrc.1999.0409 10092502

52. Bourne Y, Watson MH, Hickey MJ, Holmes W, Rocque W, Reed SI, et al. Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1. Cell. 1996;84(6):863–74. doi: 10.1016/s0092-8674(00)81065-x 8601310

53. Koivomagi M, Valk E, Venta R, Iofik A, Lepiku M, Balog ER, et al. Cascades of multisite phosphorylation control Sic1 destruction at the onset of S phase. Nature. 2011;480(7375):128–31. doi: 10.1038/nature10560 21993622

54. McGrath DA, Balog ER, Koivomagi M, Lucena R, Mai MV, Hirschi A, et al. Cks confers specificity to phosphorylation-dependent CDK signaling pathways. Nat Struct Mol Biol. 2013;20(12):1407–14. doi: 10.1038/nsmb.2707 24186063

55. Huang JY, Morley G, Li D, Whitaker M. Cdk1 phosphorylation sites on Cdc27 are required for correct chromosomal localisation and APC/C function in syncytial Drosophila embryos. J Cell Sci. 2007;120(Pt 12):1990–7. doi: 10.1242/jcs.006833 17519285

56. Parry DH, O’Farrell PH. The schedule of destruction of three mitotic cyclins can dictate the timing of events during exit from mitosis. Curr Biol. 2001;11(9):671–83. doi: 10.1016/s0960-9822(01)00204-4 11369230

57. Casas-Vila N, Bluhm A, Sayols S, Dinges N, Dejung M, Altenhein T, et al. The developmental proteome of Drosophila melanogaster. Genome Res. 2017;27(7):1273–85. doi: 10.1101/gr.213694.116 28381612

58. Bloom J, Cross FR. Multiple levels of cyclin specificity in cell-cycle control. Nat Rev Mol Cell Biol. 2007;8(2):149–60. doi: 10.1038/nrm2105 17245415

59. Lara-Gonzalez P, Moyle MW, Budrewicz J, Mendoza-Lopez J, Oegema K, Desai A. The G2-to-M Transition Is Ensured by a Dual Mechanism that Protects Cyclin B from Degradation by Cdc20-Activated APC/C. Dev Cell. 2019;51(3):313–25 e10. doi: 10.1016/j.devcel.2019.09.005 31588029

60. D’Avino PP, Archambault V, Przewloka MR, Zhang W, Laue ED, Glover DM. Isolation of protein complexes involved in mitosis and cytokinesis from Drosophila cultured cells. Methods Mol Biol. 2009;545:99–112. doi: 10.1007/978-1-60327-993-2_6 19475384

61. Dernburg A. In situ hybridization to somatic chromosomes. In: Sullivan W, Ashburner M., Hawley R.S., editor. Drosophila Protocols Cold Spring Harbour: Cold Spring Harbour Laboratory Press.; 2000. p. 25–55.

62. Kachaner D, Garrido D, Mehsen H, Normandin K, Lavoie H, Archambault V. Coupling of Polo kinase activation to nuclear localization by a bifunctional NLS is required during mitotic entry. Nat Commun. 2017;8(1):1701. doi: 10.1038/s41467-017-01876-8 29167465

Článek Inferring causal direction between two traits in the presence of horizontal pleiotropy with GWAS summary data

Článek Genetic engineering of sex chromosomes for batch cultivation of non-transgenic, sex-sorted males

Článek Differential transcript usage in the Parkinson’s disease brain

Článek Opposing functions of Fng1 and the Rpd3 HDAC complex in H4 acetylation in Fusarium graminearum

Článek Folliculin variants linked to Birt-Hogg-Dubé syndrome are targeted for proteasomal degradation

Článek TOR Complex 2- independent mutations in the regulatory PIF pocket of Gad8AKT1/SGK1 define separate branches of the stress response mechanisms in fission yeast

Článek NIGT1 family proteins exhibit dual mode DNA recognition to regulate nutrient response-associated genes in Arabidopsis

Článek Oxidative stress antagonizes fluoroquinolone drug sensitivity via the SoxR-SUF Fe-S cluster homeostatic axis

Článek A phenome-wide association study of 26 mendelian genes reveals phenotypic expressivity of common and rare variants within the general population

Článek Mms19 promotes spindle microtubule assembly in Drosophila neural stem cells

Článek Mosquito genomes are frequently invaded by transposable elements through horizontal transfer

Článek Genotype imputation using the Positional Burrows Wheeler Transform