KEGG   PATHWAY: hsa04114
Entry
hsa04114                    Pathway                                
Name
Oocyte meiosis - Homo sapiens (human)
Description
During meiosis, a single round of DNA replication is followed by two rounds of chromosome segregation, called meiosis I and meiosis II. At meiosis I, homologous chromosomes recombine and then segregate to opposite poles, while the sister chromatids segregate from each other at meoisis II. In vertebrates, immature oocytes are arrested at the PI (prophase of meiosis I). The resumption of meiosis is stimulated by progesterone, which carries the oocyte through two consecutive M-phases (MI and MII) to a second arrest at MII. The key activity driving meiotic progression is the MPF (maturation-promoting factor), a heterodimer of CDC2 (cell division cycle 2 kinase) and cyclin B. In PI-arrested oocytes, MPF is initially inactive and is activated by the dual-specificity CDC25C phosphatase as the result of new synthesis of Mos induced by progesterone. MPF activation mediates the transition from the PI arrest to MI. The subsequent decrease in MPF levels, required to exit from MI into interkinesis, is induced by a negative feedback loop, where CDC2 brings about the activation of the APC (anaphase-promoting complex), which mediates destruction of cyclin B. Re-activation of MPF for MII requires re-accumulation of high levels of cyclin B as well as the inactivation of the APC by newly synthesized Emi2 and other components of the CSF (cytostatic factor), such as cyclin E or high levels of Mos. CSF antagonizes the ubiquitin ligase activity of the APC, preventing cyclin B destruction and meiotic exit until fertilization occurs. Fertilization triggers a transient increase in cytosolic free Ca2+, which leads to CSF inactivation and cyclin B destruction through the APC. Then eggs are released from MII into the first embryonic cell cycle.
Class
Cellular Processes; Cell growth and death
Pathway map
hsa04114  Oocyte meiosis
hsa04114

Drug
D00066  Progesterone (JP18/USP/INN)
D00075  Testosterone (JAN/USP)
D00182  Norethindrone (USP)
D00289  Danazol (JP18/USP/INN)
D00327  Fluoxymesterone (JAN/USP/INN)
D00408  Methyltestosterone (JP18/USP/INN)
D00585  Mifepristone (JAN/USAN/INN)
D00949  Hydroxyprogesterone caproate (JAN/USP/INN)
D00950  Levonorgestrel (JAN/USP/INN)
D00951  Medroxyprogesterone acetate (JP18/USP)
D00952  Megestrol acetate (USP)
D00953  Norethindrone acetate (USP)
D00954  Norgestrel (JP18/USP/INN)
D00957  Testosterone cypionate (USP)
D00958  Testosterone enanthate (JP18/USP)
D00959  Testosterone propionate (JP18/USP)
D01159  Gestonorone caproate (JAN/USAN)
D01217  Dydrogesterone (JP18/USP/INN)
D01294  Ethynodiol diacetate (JAN/USP)
D01299  Chlormadinone acetate (JP18/USAN)
D01368  Cyproterone acetate (JAN/USAN)
D01374  Allylestrenol (JAN/INN)
D01533  Mestanolone (JAN/INN)
D01534  Dromostanolone propionate (USAN)
D01580  Lynestrenol (JAN/USAN)
D02367  Desogestrel (USAN/INN)
D02996  Asoprisnil (USAN/INN)
D03675  Delmadinone acetate (USAN)
D03799  Dienogest (JAN/USAN/INN)
D03917  Drospirenone (JAN/USP/INN)
D04104  Etonogestrel (USAN/INN)
D04316  Gestodene (USAN/INN)
D04885  Medrogestone (USAN/INN)
D04947  Mesterolone (USAN/INN)
D05003  Methynodiol diacetate (USAN)
D05009  Metogest (USAN/INN)
D05025  Mibolerone (USP/INN)
D05205  Norelgestromin (USP/INN)
D05207  Norethynodrel (USAN)
D05209  Norgestimate (USP/INN)
D05308  Oxogestone phenpropionate (USAN)
D05679  Quingestanol acetate (USAN)
D05680  Quingestrone (USAN/INN)
D06003  Tanaproget (USAN/INN)
D06085  Testosterone ketolaurate (USAN/INN)
D06086  Testosterone phenylacetate (USAN)
D06087  Testosterone undecanoate (USAN)
D06145  Tigestol (USAN/INN)
D06197  Tosagestin (USAN/INN)
D06235  Trimegestone (USAN/INN)
D07096  Aglepristone (INN)
D07220  Norgestrienone (INN)
D07222  Nomegestrol (USAN/INN)
D07223  Demegestone (INN)
D07670  Chlormadinone (INN)
D07766  Cyproterone (INN)
D07939  Etynodiol (INN)
D07968  Flugestone (INN)
D08052  Hydroxyprogesterone (INN)
D08053  Hydroxyprogesterone 17alfa-acetate
D08166  Medroxyprogesterone (INN)
D08167  Megestrol (INN)
D08281  Nomegestrol acetate (USAN)
D08285  Norethisterone enantate
D08431  Promegestone (INN)
D08573  Testosterone decanoate
D08574  Testosterone phenylpropionate
D09567  Ulipristal (USAN/INN)
D09687  Ulipristal acetate (JAN/USAN)
D09972  Telapristone acetate (USAN)
D10986  Segesterone acetate (USAN)
D10987  Segesterone (USAN/INN)
D11181  Vilaprisan (JAN/USAN/INN)
D12736  Lunresertib (USAN)
Other DBs
GO: 0051321
Organism
Homo sapiens (human) [GN:hsa]
Gene
3630  INS; insulin [KO:K04526]
3479  IGF1; insulin like growth factor 1 [KO:K05459]
3480  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
5241  PGR; progesterone receptor [KO:K08556]
367  AR; androgen receptor [KO:K08557]
107  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
108  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
109  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
115  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
6790  AURKA; aurora kinase A [KO:K11481] [EC:2.7.11.1]
64506  CPEB1; cytoplasmic polyadenylation element binding protein 1 [KO:K02602]
132864  CPEB2; cytoplasmic polyadenylation element binding protein 2 [KO:K02602]
22849  CPEB3; cytoplasmic polyadenylation element binding protein 3 [KO:K02602]
80315  CPEB4; cytoplasmic polyadenylation element binding protein 4 [KO:K02602]
4342  MOS; MOS proto-oncogene, serine/threonine kinase [KO:K04367] [EC:2.7.11.1]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6197  RPS6KA3; ribosomal protein S6 kinase A3 [KO:K04373] [EC:2.7.11.1]
6195  RPS6KA1; ribosomal protein S6 kinase A1 [KO:K04373] [EC:2.7.11.1]
6196  RPS6KA2; ribosomal protein S6 kinase A2 [KO:K04373] [EC:2.7.11.1]
27330  RPS6KA6; ribosomal protein S6 kinase A6 [KO:K04373] [EC:2.7.11.1]
9088  PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
7534  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
7529  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
10971  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
7531  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
7533  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
7532  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
245711  SPDYA; speedy/RINGO cell cycle regulator family member A [KO:K08694]
387778  SPDYC; speedy/RINGO cell cycle regulator family member C [KO:K08694]
100310812  SPDYE2B; speedy/RINGO cell cycle regulator family member E2B [KO:K08694]
100505767  SPDYE18; speedy/RINGO cell cycle regulator family member E18 [KO:K08694]
100996746  SPDYE11; speedy/RINGO cell cycle regulator family member E11 [KO:K08694]
102723555  SPDYE16; speedy/RINGO cell cycle regulator family member E16 [KO:K08694]
102723849  SPDYE17; speedy/RINGO cell cycle regulator family member E17 [KO:K08694]
285955  SPDYE1; speedy/RINGO cell cycle regulator family member E1 [KO:K08694]
388333  SPDYE4; speedy/RINGO cell cycle regulator family member E4 [KO:K08694]
441272  SPDYE3; speedy/RINGO cell cycle regulator family member E3 [KO:K08694]
441273  SPDYE2; speedy/RINGO cell cycle regulator family member E2 [KO:K08694]
442590  SPDYE5; speedy/RINGO cell cycle regulator family member E5 [KO:K08694]
729597  SPDYE6; speedy/RINGO cell cycle regulator family member E6 [KO:K08694]
105180391  SPDYE15; speedy/RINGO cell cycle regulator family member E15 [KO:K08694]
100101268  SPDYE12; speedy/RINGO cell cycle regulator family member E12 [KO:K08694]
124906603  putative speedy protein E9 [KO:K08694]
643862  SPDYE10; speedy/RINGO cell cycle regulator family member E10 [KO:K08694]
643909  SPDYE9; speedy/RINGO cell cycle regulator family member E9 [KO:K08694]
728524  SPDYE8; speedy/RINGO cell cycle regulator family member E8 [KO:K08694]
105180390  SPDYE13; speedy/RINGO cell cycle regulator family member E13 [KO:K08694]
641776  SPDYE14; speedy/RINGO cell cycle regulator family member E14 [KO:K08694]
983  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
1017  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
5499  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
5500  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
5501  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
9748  SLK; STE20 like kinase [KO:K08836] [EC:2.7.11.1]
5347  PLK1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
995  CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
9133  CCNB2; cyclin B2 [KO:K21770]
9978  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
8454  CUL1; cullin 1 [KO:K03347]
6500  SKP1; S-phase kinase associated protein 1 [KO:K03094]
8945  BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
23291  FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
26271  FBXO5; F-box protein 5 [KO:K10292]
64682  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
29882  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
996  CDC27; cell division cycle 27 [KO:K03350]
29945  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
51433  ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
8881  CDC16; cell division cycle 16 [KO:K03353]
51434  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
8697  CDC23; cell division cycle 23 [KO:K03355]
10393  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
51529  ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
246184  CDC26; cell division cycle 26 [KO:K03359]
25847  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
25906  ANAPC15; anaphase promoting complex subunit 15 [KO:K25228]
119504  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
991  CDC20; cell division cycle 20 [KO:K03363]
286151  FBXO43; F-box protein 43 [KO:K10318]
9232  PTTG1; PTTG1 regulator of sister chromatid separation, securin [KO:K06635]
10744  PTTG2; pituitary tumor-transforming 2 [KO:K06635]
9700  ESPL1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
9985  REC8; REC8 meiotic recombination protein [KO:K13054]
10734  STAG3; STAG3 cohesin complex component [KO:K13055]
8243  SMC1A; structural maintenance of chromosomes 1A [KO:K06636]
27127  SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
9126  SMC3; structural maintenance of chromosomes 3 [KO:K06669]
891  CCNB1; cyclin B1 [KO:K05868]
699  BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
4085  MAD2L1; mitotic arrest deficient 2 like 1 [KO:K02537]
10459  MAD2L2; mitotic arrest deficient 2 like 2 [KO:K13728]
8379  MAD1L1; mitotic arrest deficient 1 like 1 [KO:K06679]
898  CCNE1; cyclin E1 [KO:K06626]
9134  CCNE2; cyclin E2 [KO:K06626]
151648  SGO1; shugoshin 1 [KO:K11580]
5526  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
5527  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
5528  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
5529  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
5525  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
5519  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
5518  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
5515  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
5516  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
89869  PLCZ1; phospholipase C zeta 1 [KO:K05861] [EC:3.1.4.11]
3708  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
3709  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
3710  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
810  CALML3; calmodulin like 3 [KO:K02183]
805  CALM2; calmodulin 2 [KO:K02183]
808  CALM3; calmodulin 3 [KO:K02183]
801  CALM1; calmodulin 1 [KO:K02183]
163688  CALML6; calmodulin like 6 [KO:K02183]
51806  CALML5; calmodulin like 5 [KO:K02183]
91860  CALML4; calmodulin like 4 [KO:K02183]
5530  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
5532  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
5534  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
815  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
Compound
C00076  Calcium cation
C00410  Progesterone
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:16760654
  Authors
Haccard O, Jessus C
  Title
Oocyte maturation, Mos and cyclins--a matter of synthesis: two functionally redundant ways to induce meiotic maturation.
  Journal
Cell Cycle 5:1152-9 (2006)
DOI:10.4161/cc.5.11.2800
Reference
PMID:15182704
  Authors
Crane R, Gadea B, Littlepage L, Wu H, Ruderman JV
  Title
Aurora A, meiosis and mitosis.
  Journal
Biol Cell 96:215-29 (2004)
DOI:10.1016/j.biolcel.2003.09.008
Reference
PMID:15136768
  Authors
Perdiguero E, Nebreda AR
  Title
Regulation of Cdc25C activity during the meiotic G2/M transition.
  Journal
Cell Cycle 3:733-7 (2004)
DOI:10.4161/cc.3.6.906
Reference
PMID:17480229
  Authors
Perry JA, Kornbluth S
  Title
Cdc25 and Wee1: analogous opposites?
  Journal
Cell Div 2:12 (2007)
DOI:10.1186/1747-1028-2-12
Reference
PMID:15182701
  Authors
Jessus C, Ozon R
  Title
How does Xenopus oocyte acquire its competence to undergo meiotic maturation?
  Journal
Biol Cell 96:187-92 (2004)
DOI:10.1016/j.biolcel.2003.12.007
Reference
PMID:16518630
  Authors
Revenkova E, Jessberger R
  Title
Shaping meiotic prophase chromosomes: cohesins and synaptonemal complex proteins.
  Journal
Chromosoma 115:235-40 (2006)
DOI:10.1007/s00412-006-0060-x
Reference
PMID:18631137
  Authors
Belloc E, Pique M, Mendez R
  Title
Sequential waves of polyadenylation and deadenylation define a translation circuit that drives meiotic progression.
  Journal
Biochem Soc Trans 36:665-70 (2008)
DOI:10.1042/BST0360665
Reference
PMID:18598214
  Authors
Pesin JA, Orr-Weaver TL
  Title
Regulation of APC/C activators in mitosis and meiosis.
  Journal
Annu Rev Cell Dev Biol 24:475-99 (2008)
DOI:10.1146/annurev.cellbio.041408.115949
Reference
PMID:18550795
  Authors
Tang W, Wu JQ, Guo Y, Hansen DV, Perry JA, Freel CD, Nutt L, Jackson PK, Kornbluth S
  Title
Cdc2 and Mos regulate Emi2 stability to promote the meiosis I-meiosis II transition.
  Journal
Mol Biol Cell 19:3536-43 (2008)
DOI:10.1091/mbc.E08-04-0417
Reference
PMID:18946022
  Authors
Wu JQ, Kornbluth S
  Title
Across the meiotic divide - CSF activity in the post-Emi2/XErp1 era.
  Journal
J Cell Sci 121:3509-14 (2008)
DOI:10.1242/jcs.036855
Reference
PMID:16554437
  Authors
Schmidt A, Rauh NR, Nigg EA, Mayer TU
  Title
Cytostatic factor: an activity that puts the cell cycle on hold.
  Journal
J Cell Sci 119:1213-8 (2006)
DOI:10.1242/jcs.02919
Reference
PMID:18096427
  Authors
Vogt E, Kirsch-Volders M, Parry J, Eichenlaub-Ritter U
  Title
Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error.
  Journal
Mutat Res 651:14-29 (2008)
DOI:10.1016/j.mrgentox.2007.10.015
Reference
PMID:18311174
  Authors
Perry AC, Verlhac MH
  Title
Second meiotic arrest and exit in frogs and mice.
  Journal
EMBO Rep 9:246-51 (2008)
DOI:10.1038/embor.2008.22
Reference
PMID:14691134
  Authors
Tunquist BJ, Eyers PA, Chen LG, Lewellyn AL, Maller JL
  Title
Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest.
  Journal
J Cell Biol 163:1231-42 (2003)
DOI:10.1083/jcb.200306153
Reference
PMID:14517314
  Authors
Hutchins JR, Dikovskaya D, Clarke PR.
  Title
Regulation of Cdc2/cyclin B activation in Xenopus egg extracts via inhibitory phosphorylation of Cdc25C phosphatase by Ca(2+)/calmodulin-dependent protein [corrected] kinase II.
  Journal
Mol Biol Cell 14:4003-14 (2003)
DOI:10.1091/mbc.E03-02-0061
Related
pathway
hsa04010  MAPK signaling pathway
hsa04120  Ubiquitin mediated proteolysis
hsa04914  Progesterone-mediated oocyte maturation
KO pathway
ko04114   
LinkDB

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