Time-Dependent Quantitative Multicomponent Control of the G₁-S Network by the Stress-Activated Protein Kinase Hog1 upon Osmostress

Miquel Àngel Adrover, Zhike Zi, Alba Duch, Jörg Schaber, Alberto González-Novo, Javier Jimenez, Mariona Nadal-Ribelles, Josep Clotet, Edda Klipp,* Francesc Posas*

*To whom correspondence should be addressed. E-mail: edda.klipp{at}rz.hu-berlin.de (E.K.); francesc.posas{at}upf.edu (F.P.)

This PDF file includes:

• Model Description
• Table S1. Overview of experimental design.
• Table S2. SD of the estimated parameters.
• Table S3. Initial conditions of the state variables.
• Table S4. Complete list of model parameter values.
• References
• Fig. S1. The timing relationship between Sic1, Cln2, replication, and budding is maintained for stronger stress.
• Fig. S2. Hog1 activation correlates with a cell cycle arrest in G₁ during osmostress in cells synchronized by elutriation.
• Fig. S3. Patterns of cyclin production and Sic1 degradation are altered during osmostress.
• Fig. S4. Hog1 activation delays Clb5 production when cells are stressed before Start in a second cell cycle.
• Fig. S5. Osmostress delays onset of mRNA production of MBF-dependent genes, as well as Clb5 transcripts and protein.
• Fig. S6. The coarse-grained black box model describing Cln2 and Clb5 production.
• Fig. S7. Comparison of model simulation result to experimental data used for parameter estimation (in-sample fit).
• Fig. S8. Validation of model with additional experimental data under other conditions (out-sample fit).
• Fig. S9. Predictions for the in silico Sic1^T173A mutant in response to osmotic stress.
• Fig. S10. Predictions for the in silico knockout for Cln2 production in response to osmotic stress.
• Fig. S11. Predictions for the in silico knockout for Clb5 production in response to osmotic stress.
• Fig. S12. Inactivation of Sln1 leads to accumulation of Sic1- and Hog1-mediated G₁ arrest.
• Fig. S13. Predictions for GAL1::CLN2 (Cln2 overexpression) and GAL1::CLB5 (Clb5 overexpression).
• Fig. S14. Effect of ectopic expression of CLN2 and CLB5 from the GAL1 promoter on G₁ arrest in response to osmotic stress.
• Fig. S15. Regulation of Clb5 and the onset of replication upon osmostress are independent of the down-regulation of CLN2.

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Other Supplementary Material for this manuscript includes the following:

• SBML Model S1. Final_Model_for_noStress.xml
• SBML Model S2. Final_Model_for_Stress_Conditions.xml

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© 2011 American Association for the Advancement of Science