Abstract
Gametogenesis and fertilization are the key events in sexual reproduction. In the female, meiosis results in a large oocyte that is competent for fertilization and fundamental for the success of early embryonic development. Progression through meiosis is monitored by fine regulatory mechanisms. In this review, we focus on one of the most well-known regulatory elements, the E3 ligase APC/C, which mediates proteolytic degradation of a number of important substrates via the ubiquitin proteasome pathway (UPP). The UPP also indirectly regulates protein synthesis by affecting proteins involved in RNA metabolism, a process that is paramount for the transcriptionally silent oocyte. During the past few years, more evidence has accumulated to suggest that the UPP has an important role in zona pellucida penetration and gamete fusion in mammals. This review focuses on the function of the UPP in regulating oocyte meiotic maturation in mammals, with special attention to its role in chromosome segregation and polar body extrusion, its role in the acquisition of meiotic/developmental competence and recent advances in our understanding of the UPP role in fertilization.
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Baba T, Azuma S, Kashiwabara S, Toyoda Y (1994) Sperm from mice carrying a targeted mutation of the acrosin gene can penetrate the oocyte zona pellucida and effect fertilization. J Biol Chem 269:31845–31849
Baker MA, Hetherington L, Reeves G, Müller J, Aitken RJ (2008a) The rat sperm proteome characterized via IPG strip prefractionation and LC-MS/MS identification. Proteomics 8:2312–2321
Baker MA, Hetherington L, Reeves GM, Aitken RJ (2008b) The mouse sperm proteome characterized via IPG strip prefractionation and LC-MS/MS identification. Proteomics 8:1720–1730
Baska KM, Manandhar G, Feng D, Agca Y, Tengowski MW, Sutovsky M, Yi YJ, Sutovsky P (2008) Mechanism of extracellular ubiquitination in the mammalian epididymis. J Cell Physiol 215:684–696
Benmaamar R, Pagano M (2005) Involvement of the SCF complex in the control of Cdh1 degradation in S-phase. Cell Cycle 4:1230–1232
Bhat KP, Greer SF (2011) Proteolytic and non-proteolytic roles of ubiquitin and the ubiquitin proteasome system in transcriptional regulation. Biochim Biophys Acta 1809:150–155
Biały LP, Ziemba HT, Marianowski P, Fracki S, Bury M, Wójcik C (2001) Localization of a proteasomal antigen in human spermatozoa: immunohistochemical electron microscopic study. Folia Histochem Cytobiol 39:129–130
Blondin P, Sirard MA (1995) Oocyte and follicular morphology as determining characteristics for developmental competence in bovine oocytes. Mol Reprod Dev 41:54–62
Chakravarty S, Bansal P, Sutovsky P, Gupta SK (2008) Role of proteasomal activity in the induction of acrosomal exocytosis in human spermatozoa. Reprod Biomed Online 16:391–400
Dawson IA, Roth S, Artavanis-Tsakonas S (1995) 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 129:725–737
DeAntoni A, Sala V, Musacchio A (2005) Explaining the oligomerization properties of the spindle assembly checkpoint protein Mad2. Philos Trans R Soc Lond B 360:637–647, discussion 447–638
Dekel N (2005) Cellular, biochemical and molecular mechanisms regulating oocyte maturation. Mol Cell Endocrinol 234:19–25
Eldridge AG, Loktev AV, Hansen DV, Verschuren EW, Reimann JD, Jackson PK (2006) The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1. Cell 124:367–380
Fang S, Weissman AM (2004) A field guide to ubiquitylation. Cell Mol Life Sci 61:1546–1561
Fischer KA, Van Leyen K, Lovercamp KW, Manandhar G, Sutovsky M, Feng D, Safranski T, Sutovsky P (2005) 15-Lipoxygenase is a component of the mammalian sperm cytoplasmic droplet. Reproduction 130:213–222
Flemr M, Ma J, Schultz RM, Svoboda P (2010) P-body loss is concomitant with formation of a messenger RNA storage domain in mouse oocytes. Biol Reprod 82:1008–1017
Garner E, Smogorzewska A (2011) Ubiquitylation and the Fanconi anemia pathway. FEBS Lett, in press (doi:10.1016/j.febslet.2011.04.078)
Gautier J, Minshull J, Lohka M, Glotzer M, Hunt T, Maller JL (1990) Cyclin is a component of maturation-promoting factor from Xenopus. Cell 60:487–494
Glotzer M, Murray AW, Kirschner MW (1991) Cyclin is degraded by the ubiquitin pathway. Nature 349:132–138
Guterman A, Glickman MH (2004) Deubiquitinating enzymes are IN/(trinsic to proteasome function). Curr Protein Pept Sci 5:201–211
Hake LE, Richter JD (1994) CPEB is a specificity factor that mediates cytoplasmic polyadenylation during Xenopus oocyte maturation. Cell 79:617–627
Hansen DV, Tung JJ, Jackson PK (2006) CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit. Proc Natl Acad Sci USA 103:608–613
Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479
Hershko A, Ganoth D, Pehrson J, Palazzo RE, Cohen LH (1991) Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts. J Biol Chem 266:16376–16379
Hicke L (2001) Protein regulation by monoubiquitin. Nat Rev Mol Cell Biol 2:195–201
Huo LJ, Fan HY, Liang CG, Yu LZ, Zhong ZS, Chen DY, Sun QY (2004) Regulation of ubiquitin-proteasome pathway on pig oocyte meiotic maturation and fertilization. Biol Reprod 71:853–862
Kawano N, Kang W, Yamashita M, Koga Y, Yamazaki T, Hata T, Miyado K, Baba T (2010) Mice lacking two sperm serine proteases, ACR and PRSS21, are subfertile, but the mutant sperm are infertile in vitro. Biol Reprod 83:359–369
Kim HM, Yu Y, Cheng Y (2011) Structure characterization of the 26S proteasome. Biochim Biophys Acta 1809:67–79
Labbé JC, Capony JP, Caput D, Cavadore JC, Derancourt J, Kaghad M, Lelias JM, Picard A, Dorée M (1989) MPF from starfish oocytes at first meiotic metaphase is a heterodimer containing one molecule of cdc2 and one molecule of cyclin B. EMBO J 8:3053–3058
Lequarre AS, Vigneron C, Ribaucour F, Holm P, Donnay I, Dalbiès-Tran R, Callesen H, Mermillod P (2005) Influence of antral follicle size on oocyte characteristics and embryo development in the bovine. Theriogenology 63:841–859
Liu J, Maller JL (2005) Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor. Curr Biol 15:1458–1468
Lohka MJ (1989) Mitotic control by metaphase-promoting factor and cdc proteins. J Cell Sci 92:131–135
Madgwick S, Hansen DV, Levasseur M, Jackson PK, Jones KT (2006) Mouse Emi2 is required to enter meiosis II by reestablishing cyclin B1 during interkinesis. J Cell Biol 174:791–801
Marangos P, Carroll J (2008) Securin regulates entry into M-phase by modulating the stability of cyclin B. Nat Cell Biol 10:445–451
Marangos P, Verschuren EW, Chen R, Jackson PK, Carroll J (2007) Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1). J Cell Biol 176:65–75
McRorie RA, Williams WL (1974) Biochemistry of mammalian fertilization. Annu Rev Biochem 43:777–803
Mendez R, Barnard D, Richter JD (2002) Differential mRNA translation and meiotic progression require Cdc2-mediated CPEB destruction. EMBO J 21:1833–1844
Mermillod P, Oussaid B, Cognié Y (1999) Aspects of follicular and oocyte maturation that affect the developmental potential of embryos. J Reprod Fertil Suppl 54:449–460
Morales P, Kong M, Pizarro E, Pasten C (2003) Participation of the sperm proteasome in human fertilization. Hum Reprod 18:1010–1017
Morales P, Pizarro E, Kong M, Jara M (2004) Extracellular localization of proteasomes in human sperm. Mol Reprod Dev 68:115–124
Mtango NR, Latham KE (2007) Ubiquitin proteasome pathway gene expression varies in rhesus monkey oocytes and embryos of different developmental potential. Physiol Genomics 31:1–14
Mtango NR, Sutovsky M, Susor A, Zhong Z, Latham KE, Sutovsky P (2011) Essential role of maternal UCHL1 and UCHL3 in fertilization and preimplantation embryo development. J Cell Physiol, in press (doi:10.1002/jcp.22876)
Ohta T, Sato K, Wu W (2011) The BRCA1 ubiquitin ligase and homologous recombination repair. FEBS Lett, in press (doi:10.1016/j.febslet.2011.05.005)
Pavlok A, Lucas-Hahn A, Niemann H (1992) Fertilization and developmental competence of bovine oocytes derived from different categories of antral follicles. Mol Reprod Dev 31:63–67
Pesin JA, Orr-Weaver TL (2008) Regulation of APC/C activators in mitosis and meiosis. Annu Rev Cell Dev Biol 24:475–499
Peters JM (2002) The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol Cell 9:931–943
Peters JM (2006) The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 7:644–656
Prinz S, Hwang ES, Visintin R, Amon A (1998) The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and Cdc27 during S phase and early mitosis. Curr Biol 8:750–760
Racedo SE, Wrenzycki C, Herrmann D, Salamone D, Niemann H (2008) Effects of follicle size and stages of maturation on mRNA expression in bovine in vitro matured oocytes. Mol Reprod Dev 75:17–25
Racedo SE, Branzini MC, Salamone D, Wójcik C, Rawe VY, Niemann H (2009) Dynamics of microtubules, motor proteins and 20S proteasomes during bovine oocyte IVM. Reprod Fertil Dev 21:304–312
Raghu HM, Nandi S, Reddy SM (2002) Follicle size and oocyte diameter in relation to developmental competence of buffalo oocytes in vitro. Reprod Fertil Dev 14:55–61
Reis A, Chang HY, Levasseur M, Jones KT (2006a) APCcdh1 activity in mouse oocytes prevents entry into the first meiotic division. Nat Cell Biol 8:539–540
Reis A, Levasseur M, Chang HY, Elliott DJ, Jones KT (2006b) The CRY box: a second APCcdh1-dependent degron in mammalian cdc20. EMBO Rep 7:1040–1045
Reis A, Madgwick S, Chang HY, Nabti I, Levasseur M, Jones KT (2007) Prometaphase APCcdh1 activity prevents non-disjunction in mammalian oocytes. Nat Cell Biol 9:1192–1198
Reverte CG, Ahearn MD, Hake LE (2001) CPEB degradation during Xenopus oocyte maturation requires a PEST domain and the 26S proteasome. Dev Biol 231:447–458
Richter JD (2007) CPEB: a life in translation. Trends Biochem Sci 32:279–285
Rosen MP, Shen S, Dobson AT, Rinaudo PF, McCulloch CE, Cedars MI (2008) A quantitative assessment of follicle size on oocyte developmental competence. Fertil Steril 90:684–690
Sakai N, Sawada MT, Sawada H (2004) Non-traditional roles of ubiquitin-proteasome system in fertilization and gametogenesis. Int J Biochem Cell Biol 36:776–784
Sawada H, Pinto MR, De Santis R (1998) Participation of sperm proteasome in fertilization of the phlebobranch ascidian Ciona intestinalis. Mol Reprod Dev 50:493–498
Sawada H, Sakai N, Abe Y, Tanaka E, Takahashi Y, Fujino J, Kodama E, Takizawa S, Yokosawa H (2002) Extracellular ubiquitination and proteasome-mediated degradation of the ascidian sperm receptor. Proc Natl Acad Sci USA 99:1223–1228
Schwab M, Lutum AS, Seufert W (1997) Yeast Hct1 is a regulator of Clb2 cyclin proteolysis. Cell 90:683–693
Sekiguchi S, Kwon J, Yoshida E, Hamasaki H, Ichinose S, Hideshima M, Kuraoka M, Takahashi A, Ishii Y, Kyuwa S, Wada K, Yoshikawa Y (2006) Localization of ubiquitin C-terminal hydrolase L1 in mouse ova and its function in the plasma membrane to block polyspermy. Am J Pathol 169:1722–1729
Setoyama D, Yamashita M, Sagata N (2007) Mechanism of degradation of CPEB during Xenopus oocyte maturation. Proc Natl Acad Sci USA 104:18001–18006
Sigrist SJ, Lehner CF (1997) Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles. Cell 90:671–681
Sixt SU, Beiderlinden M, Jennissen HP, Peters J (2007) Extracellular proteasome in the human alveolar space: a new housekeeping enzyme? Am J Physiol Lung Cell Mol Physiol 292:L1280–L1288
Susor A, Ellederova Z, Jelinkova L, Halada P, Kavan D, Kubelka M, Kovarova H (2007) Proteomic analysis of porcine oocytes during in vitro maturation reveals essential role for the ubiquitin C-terminal hydrolase-L1. Reproduction 134:559–568
Susor A, Liskova L, Toralova T, Pavlok A, Pivonkova K, Karabinova P, Lopatarova M, Sutovsky P, Kubelka M (2010) Role of ubiquitin C-terminal hydrolase-L1 in antipolyspermy defense of mammalian oocytes. Biol Reprod 82:1151–1161
Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G (2000) Ubiquitinated sperm mitochondria, selective proteolysis, and the regulation of mitochondrial inheritance in mammalian embryos. Biol Reprod 63:582–590
Sutovsky P, Manandhar G, McCauley TC, Caamaño JN, Sutovsky M, Thompson WE, Day BN (2004) Proteasomal interference prevents zona pellucida penetration and fertilization in mammals. Biol Reprod 71:1625–1637
Thom G, Minshall N, Git A, Argasinska J, Standart N (2003) Role of cdc2 kinase phosphorylation and conserved N-terminal proteolysis motifs in cytoplasmic polyadenylation-element-binding protein (CPEB) complex dissociation and degradation. Biochem J 370:91–100
Tipler CP, Hutchon SP, Hendil K, Tanaka K, Fishel S, Mayer RJ (1997) Purification and characterization of 26S proteasomes from human and mouse spermatozoa. Mol Hum Reprod 3:1053–1060
Trounson A, Anderiesz C, Jones GM, Kausche A, Lolatgis N, Wood C (1998) Oocyte maturation. Hum Reprod 13(Suppl 3):52–62, discussion 71–55
Tunquist BJ, Maller JL (2003) Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs. Genes Dev 17:683–710
Ulrich HD (2011) Timing and spacing of ubiquitin-dependent DNA damage bypass. FEBS Lett, in press (doi:10.1016/j.febslet.2011.05.028)
Uzbekova S, Arlot-Bonnemains Y, Dupont J, Dalbiès-Tran R, Papillier P, Pennetier S, Thélie A, Perreau C, Mermillod P, Prigent C, Uzbekov R (2008) Spatio-temporal expression patterns of aurora kinases a, B, and C and cytoplasmic polyadenylation-element-binding protein in bovine oocytes during meiotic maturation. Biol Reprod 78:218–233
Verlhac MH, Terret ME, Pintard L (2010) Control of the oocyte-to-embryo transition by the ubiquitin-proteolytic system in mouse and C. elegans. Nat Rev Cell Biol 22:1–6
Vink M, Simonetta M, Transidico P, Ferrari K, Mapelli M, De Antoni A, Massimiliano L, Ciliberto A, Faretta M, Salmon ED, Musacchio A (2006) In vitro FRAP identifies the minimal requirements for Mad2 kinetochore dynamics. Curr Biol 16:755–766
Visintin R, Prinz S, Amon A (1997) CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science 278:460–463
Wojcik C, Benchaib M, Lornage J, Czyba JC, Guerin JF (2000) Proteasomes in human spermatozoa. Int J Androl 23:169–177
Yamagata K, Murayama K, Kohno N, Kashiwabara S, Baba T (1998a) p-Aminobenzamidine-sensitive acrosomal protease(s) other than acrosin serve the sperm penetration of the egg zona pellucida in mouse. Zygote 6:311–319
Yamagata K, Murayama K, Okabe M, Toshimori K, Nakanishi T, Kashiwabara S, Baba T (1998b) Acrosin accelerates the dispersal of sperm acrosomal proteins during acrosome reaction. J Biol Chem 273:10470–10474
Yamamuro T, Kano K, Naito K (2008) Functions of FZR1 and CDC20, activators of the anaphase-promoting complex, during meiotic maturation of swine oocytes. Biol Reprod 79:1202–1209
Yi YJ, Manandhar G, Sutovsky M, Li R, Jonáková V, Oko R, Park CS, Prather RS, Sutovsky P (2007) Ubiquitin C-terminal hydrolase-activity is involved in sperm acrosomal function and anti-polyspermy defense during porcine fertilization. Biol Reprod 77:780–793
Yi YJ, Manandhar G, Sutovsky M, Jonáková V, Park CS, Sutovsky P (2010) Inhibition of 19S proteasomal regulatory complex subunit PSMD8 increases polyspermy during porcine fertilization in vitro. J Reprod Immunol 84:154–163
Ziemba H, Biały LP, Fracki S, Bablok L, Wójcik C (2002) Proteasome localization and ultrastructure of spermatozoa from patients with varicocele–immunoelectron microscopic study. Folia Histochem Cytobiol 40:169–170
Zimmerman SW, Manandhar G, Yi YJ, Gupta SK, Sutovsky M, Odhiambo JF, Powell MD, Miller DJ, Sutovsky P (2011) Sperm proteasomes degrade sperm receptor on the egg zona pellucida during mammalian fertilization. PLoS One 6:e17256
Acknowledgment
We would like to thank Dr. Peter Sutovsky for helpful comments on the manuscript, Dr. Matthew S. Cook for careful reading of the manuscript and Ms. Kathy Craighead for manuscript editing. This work was supported by P502/10/0944 for M.K. and P.K. was supported by grant 204/09/H084, both from the Czech Science Foundation.
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Karabinova, P., Kubelka, M. & Susor, A. Proteasomal degradation of ubiquitinated proteins in oocyte meiosis and fertilization in mammals. Cell Tissue Res 346, 1–9 (2011). https://doi.org/10.1007/s00441-011-1235-1
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DOI: https://doi.org/10.1007/s00441-011-1235-1