Queralt2006 - Initiation of mitotic exit by downregulation of PP2A in budding yeast
Mathematical model of mitotic exit in budding yeast.
- Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast.
- Queralt E, Lehane C, Novak B, Uhlmann F
- Cell , 5/ 2006 , Volume 125 , pages: 719-732 , PubMed ID: 16713564
- Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
- After anaphase, the high mitotic cyclin-dependent kinase (Cdk) activity is downregulated to promote exit from mitosis. To this end, in the budding yeast S. cerevisiae, the Cdk counteracting phosphatase Cdc14 is activated. In metaphase, Cdc14 is kept inactive in the nucleolus by its inhibitor Net1. During anaphase, Cdk- and Polo-dependent phosphorylation of Net1 is thought to release active Cdc14. How Net1 is phosphorylated specifically in anaphase, when mitotic kinase activity starts to decline, has remained unexplained. Here, we show that PP2A(Cdc55) phosphatase keeps Net1 underphosphorylated in metaphase. The sister chromatid-separating protease separase, activated at anaphase onset, interacts with and downregulates PP2A(Cdc55), thereby facilitating Cdk-dependent Net1 phosphorylation. PP2A(Cdc55) downregulation also promotes phosphorylation of Bfa1, contributing to activation of the "mitotic exit network" that sustains Cdc14 as Cdk activity declines. These findings allow us to present a new quantitative model for mitotic exit in budding yeast.
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Matthieu MAIRE, Krishna Kumar Tiwari
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|queralt2006_final.xml||SBML L2V4 representation of Queralt2006 - Initiation of mitotic exit by downregulation of PP2A in budding yeast||157.41 KB||Preview | Download|
|queralt2006_final.cps||Copasi file (version 4.23 Build 184) for reproducing figure 7B in the reference publication.||215.33 KB||Preview | Download|
|queralt2006_final.sedml||SEDML file for reproducing figure 7B in the reference publication.||5.97 KB||Preview | Download|
- Model originally submitted by : Matthieu MAIRE
- Submitted: Sep 6, 2018 1:39:56 PM
- Last Modified: May 18, 2020 12:22:02 PM
- Submitted on: May 18, 2020 12:22:02 PM
- Submitted by: Krishna Kumar Tiwari
- With comment: Automatically added model identifier BIOMD0000000953
- Submitted on: Sep 6, 2018 1:39:56 PM
- Submitted by: Matthieu MAIRE
- With comment: Edited model metadata online.
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: Variable used inside SBML models
Nucleolar protein NET1
Cell division control protein 15
Securin ; Separin ; protein complex
Cyclin-dependent kinase 1
Cell cycle serine/threonine-protein kinase CDC5/MSD2
|net1 => ; cdk, men, net1cdc14||nucleus*(kp*cdk+kp_p*men)*net1/(Jnet+net1+net1cdc14)||kp = 0.4; kp_p = 2.0; Jnet = 0.2|
|=> cdc15; cdc14, cdc15_total||nucleus*(ka_cdc15+ka_cdc15_p*cdc14)*(cdc15_total-cdc15)/((J_cdc15+cdc15_total)-cdc15)||ka_cdc15_p = 0.5; ka_cdc15 = 0.02; J_cdc15 = 0.2|
|securin = securin_total-securin_separase|||||
|securin_separase => ; cdc20||nucleus*(ld_securin+kd_separase+kd_securin+kd_securin_p*cdc20)*securin_separase||kd_separase = 0.004; ld_securin = 1.0; kd_securin = 0.05; kd_securin_p = 2.0|
|=> net1; cdc14, pp2a, net1p||nucleus*(kd_p*cdc14+kd*pp2a)*net1p/(Jnet+net1p)||kd = 0.45; Jnet = 0.2; kd_p = 0.1|
|cdk = clb2/(1+Inh)|||||
|polo =>||nucleus*ki_polo*polo/(J_polo+polo)||J_polo = 0.25; ki_polo = 0.1|
|=> men; tem1, cdc15||nucleus*la_men*(tem1-men)*(cdc15-men)||la_men = 10.0|
|men =>||nucleus*ld_men*men||ld_men = 0.01|
|=> clb2||nucleus*ks_clb2||ks_clb2 = 0.03|
(added: 06 Sep 2018, 14:00:16, updated: 06 Sep 2018, 14:00:16)