Oocyte meiosis - Homo sapiens (human)

Curator(s): Julie Conway

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.    
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Oocyte meiosis - Homo sapiens (human) insulin INS insulin-like growth factor 1 receptor IGF1R INS->IGF1R node1 1 IGF1R->node1 IGF1R cAMP IGF1R->cAMP progesterone receptor PGR androgen receptor AR AR->cAMP PKA cAMP->PKA node2 1 PKA->node2 PKA node12 CDC25C(1) PKA->node12 +p Early translation of maternal mRNAs PKA->Early translation of maternal mRNAs AC AC->cAMP Progesterone Progesterone->PGR Progesterone->AR node3 Aurora-A Progesterone->node3 node32 ? Progesterone->node32 node4 CPEB(1) node3->node4 +p node16 CPEB(2) node3->node16 +P node4->Early translation of maternal mRNAs v-mos Moloney murine sarcoma viral oncogene homolog MOS MEK1 MOS->MEK1 +p myelin transcription factor 1 MYT1 MOS->MYT1 +p node5 2 MEK1->node5 MEK1 P42MAPK MEK1->P42MAPK +p node6 15 P42MAPK->node6 P42MAPK node10 RSK1/2 P42MAPK->node10 +p EMI1 node27 APC/C CDC20 EMI1->node27 node7 C3H-4 node7->EMI1 Late translation of maternal mRNAs node7->Late translation of maternal mRNAs node8 SCF beta-TrCP node8->EMI1 node9 1 MYT1->node9 MYT1 node35 CYCB2/B5 CDC2 MYT1->node35 +p node10->MYT1 +p budding uninhibited by benzimidazoles 1 homolog (yeast) BUB1 node10->BUB1 +p node29 EMI2(2) node10->node29 +p node11 RINGO CDC2 node11->node12 +p node12->node35 -p cyclin-dependent kinase 2 CDK2 CDK2->node12 +p node13 1 XP38Y XP38Y->node12 +p XP38Y->node13 XP38Y PP1 PP1->node12 -p node14 PLK1(1) node14->node12 +p node15 14-3 -3 node15->node12 PLKK1 PLKK1->node14 +p node28 Late-late translation of maternal mRNAs node16->node28 node16->Late translation of maternal mRNAs node17 EMI2(1) node36 APC/C CDC20 node17->node36 node18 MAD1/2 BUB1->node18 SGO BUB1->SGO node26 APC/C CDC20 node18->node26 +p node19 B56 PP2A SGO->node19 node20 REC8 STAG3 SMC1 SMC3 node19->node20 Meiosis II exit node20->Meiosis II exit node21 Separase(2) node21->node20 Pericentromeric cohesion node22 Securin(2) node22->node21 node23 CYCE CDK2 node23->node26 +p node24 2 node25 CYCB1/B4 CDC2 node25->node24 CYCB1/B4~CDC2 Meiosis II arrest node25->Meiosis II arrest node25->node29 +p node26->node22 +u node26->node25 +u Meiosis II resumption node26->Meiosis II resumption Degradation of CycB node26->node35 +u node27->node35 +u node28->node17 node28->node23 node28->node29 Late translation of maternal mRNAs->node25 MPF Late translation of maternal mRNAs->node28 Meiosis I progression Prevent DNA replication Bipolar spindle formation Early translation of maternal mRNAs->MOS Early translation of maternal mRNAs->EMI1 Early translation of maternal mRNAs->node7 Early translation of maternal mRNAs->node11 Early translation of maternal mRNAs->node35 CAN CAN->node26 -p CALM CALM->CAN CAMKII CALM->CAMKII CAMKII->node29 +p node33 CDC25C(2) CAMKII->node33 +p node29->node26 IP3R node31 Ca2+ IP3R->node31 node30 PLC-zeta IP3 node30->IP3 Fertilization Fertilization->node30 node31->CALM IP3->IP3R node32->AC Delay to reentry into meiosis node33->Delay to reentry into meiosis node34 2 node35->node12 +p node35->PLKK1 +p node35->node16 +p node35->Meiosis I progression node35->Prevent DNA replication node35->Bipolar spindle formation node35->node34 CYCB2/B5~CDC2 node36->node35 +u node37 Securin(1) node36->node37 +u Meiosis I exit node36->Meiosis I exit node38 Separase(1) node37->node38 node39 REC8 STAG3 SMC1 SMC3 node38->node39 Arm cohesion node39->Meiosis I exit node40 SCF beta-TrCP node40->node17 node41 SCF beta-TrCP node41->node29 node42 PLK1(2) node42->node16 +p node43 PLK1(3) node43->node29 +p print "