KEGG   PATHWAY: hsa04114Help
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
BRITE hierarchy
Pathway map
Oocyte meiosis
hsa04114

All organismsOrtholog table
Module
SCF-BTRC complex [PATH:hsa04114]
APC/C complex [PATH:hsa04114]
Disease
H00574  
Coffin-Lowry syndrome (CLS)
H00608  
46,XY disorders of sex development (Disorders in androgen synthesis or action)
H00631  
Cornelia de Lange syndrome (CdLS)
H01274  
Growth delay due to insulin-like growth factor I resistance
Drug
D00066  
Progesterone (JP17/USP/INN)
D00182  
Norethindrone (USP)
D00289  
Danazol (JP17/USP/INN)
D00585  
Mifepristone (JAN/USAN/INN)
D00949  
Hydroxyprogesterone caproate (JAN/USP/INN)
D00950  
Levonorgestrel (JAN/USP/INN)
D00951  
Medroxyprogesterone acetate (JP17/USP)
D00952  
Megestrol acetate (USAN)
D00953  
Norethindrone acetate (USP)
D00954  
Norgestrel (JP17/USP/INN)
D01159  
Gestonorone caproate (JAN/USAN)
D01217  
Dydrogesterone (JP17/USP/INN)
D01294  
Ethynodiol diacetate (JAN/USP)
D01299  
Chlormadinone acetate (JP17/USAN)
D01374  
Allylestrenol (JAN/INN)
D01580  
Lynestrenol (JAN/USAN)
D02367  
Desogestrel (USAN/INN)
D02996  
Asoprisnil (USAN/INN)
D03297  
Mecasermin (USAN/INN)
D03799  
Dienogest (JAN/USAN/INN)
D04104  
Etonogestrel (USAN/INN)
D04316  
Gestodene (USAN/INN)
D04870  
Mecasermin rinfabate (USAN/INN)
D04885  
Medrogestone (USAN/INN)
D04947  
Mesterolone (USAN/INN)
D05003  
Methynodiol diacetate (USAN)
D05025  
Mibolerone (USP/INN)
D05209  
Norgestimate (USP/INN)
D05679  
Quingestanol acetate (USAN)
D07220  
Norgestrienone (INN)
D07222  
Nomegestrol (USAN/INN)
D07223  
Demegestone (INN)
D07670  
Chlormadinone (INN)
D07939  
Etynodiol (INN)
D08052  
Hydroxyprogesterone (INN)
D08053  
Hydroxyprogesterone 17alfa-acetate
D08166  
Medroxyprogesterone (INN)
D08167  
Megestrol (INN)
D08281  
Nomegestrol acetate (USAN)
D08285  
Norethisterone enantate
D08431  
Promegestone (INN)
D09972  
Telapristone acetate (USAN)
Other DBs
BSID: 
GO: 
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; v-mos Moloney murine sarcoma viral oncogene homolog [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]
SPDYE2B; speedy/RINGO cell cycle regulator family member E2B [KO:K08694]
SPDYE18; speedy/RINGO cell cycle regulator family member E18 [KO:K08694]
SPDYE11; speedy/RINGO cell cycle regulator family member E11 [KO:K08694]
SPDYE16; speedy/RINGO cell cycle regulator family member E16 [KO:K08694]
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]
983  
CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.23 2.7.11.22]
1017  
CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
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]
9978  
RBX1; ring-box 1 [KO:K03868]
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]
991  
CDC20; cell division cycle 20 [KO:K03363]
286151  
FBXO43; F-box protein 43 [KO:K10318]
9232  
PTTG1; pituitary tumor-transforming 1 [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; stromal antigen 3 [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]
699  
BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
4085  
MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
10459  
MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
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]
6300  
MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
891  
CCNB1; cyclin B1 [KO:K05868]
9133  
CCNB2; cyclin B2 [KO:K05868]
Compound
C00076  
Calcium cation
C00410  
Progesterone
C00575  
3',5'-Cyclic AMP
C01245  
D-myo-Inositol 1,4,5-trisphosphate
Reference
  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)
Reference
  Authors
Crane R, Gadea B, Littlepage L, Wu H, Ruderman JV
  Title
Aurora A, meiosis and mitosis.
  Journal
Biol Cell 96:215-29 (2004)
Reference
  Authors
Perdiguero E, Nebreda AR
  Title
Regulation of Cdc25C activity during the meiotic G2/M transition.
  Journal
Cell Cycle 3:733-7 (2004)
Reference
  Authors
Perry JA, Kornbluth S
  Title
Cdc25 and Wee1: analogous opposites?
  Journal
Cell Div 2:12 (2007)
Reference
  Authors
Jessus C, Ozon R
  Title
How does Xenopus oocyte acquire its competence to undergo meiotic maturation?
  Journal
Biol Cell 96:187-92 (2004)
Reference
  Authors
Revenkova E, Jessberger R
  Title
Shaping meiotic prophase chromosomes: cohesins and synaptonemal complex proteins.
  Journal
Chromosoma 115:235-40 (2006)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  Authors
Perry AC, Verlhac MH
  Title
Second meiotic arrest and exit in frogs and mice.
  Journal
EMBO Rep 9:246-51 (2008)
Reference
  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)
Reference
  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)
KO pathway
 

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