The Dcr2p phosphatase destabilizes Sic1p in Saccharomyces cerevisiae

Pathak, Ritu; Blank, Heidi M.; Guo, Jingyi; Ellis, Sarah; Polymenis, Michael

doi:10.1016/j.bbrc.2007.07.092

Cited by 9 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, cells that were shifted to pheromone one step earlier, exhibited only a decline in the level of Sic1 (Figure 5B, step 17). This result points to Sic1 as the indicator for commitment, as previously suggested [31,32]. …”

Section: Resultssupporting

confidence: 83%

The effective application of a discrete transition model to explore cell-cycle regulation in yeast

et al. 2013

View full text Add to dashboard Cite

BackgroundBench biologists often do not take part in the development of computational models for their systems, and therefore, they frequently employ them as “black-boxes”. Our aim was to construct and test a model that does not depend on the availability of quantitative data, and can be directly used without a need for intensive computational background.ResultsWe present a discrete transition model. We used cell-cycle in budding yeast as a paradigm for a complex network, demonstrating phenomena such as sequential protein expression and activity, and cell-cycle oscillation. The structure of the network was validated by its response to computational perturbations such as mutations, and its response to mating-pheromone or nitrogen depletion. The model has a strong predicative capability, demonstrating how the activity of a specific transcription factor, Hcm1, is regulated, and what determines commitment of cells to enter and complete the cell-cycle.ConclusionThe model presented herein is intuitive, yet is expressive enough to elucidate the intrinsic structure and qualitative behavior of large and complex regulatory networks. Moreover our model allowed us to examine multiple hypotheses in a simple and intuitive manner, giving rise to testable predictions. This methodology can be easily integrated as a useful approach for the study of networks, enriching experimental biology with computational insights.

show abstract

Section: Resultssupporting

confidence: 83%

The effective application of a discrete transition model to explore cell-cycle regulation in yeast

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Sic1 is a stoichiometric inhibitor of the B-type cyclins responsible for initiating replication (Schwob et al, 1994) and has been suggested to also play a role in cell cycle commitment (Pathak et al, 2007). To investigate the potential role of Sic1 at Start , we created a strain expressing Whi5-mCherry and Sic1-GFP from their endogenous loci.…”

Section: Resultsmentioning

confidence: 99%

Distinct Interactions Select and Maintain a Specific Cell Fate

2011

View full text Add to dashboard Cite

The ability to specify and maintain discrete cell fates is essential for development. However, the dynamics underlying selection and stability of distinct cell types remains poorly understood. Here, we provide a quantitative single-cell analysis of commitment dynamics during the mating-mitosis switch in budding yeast. Commitment to division corresponds precisely to activating the G1 cyclin positive feedback loop in competition with the cyclin inhibitor Far1. Cyclin-dependent phosphorylation and inhibition of the mating pathway scaffold Ste5 is required to ensure exclusive expression of the mitotic transcriptional program after cell cycle commitment. Failure to commit exclusively results in coexpression of both cell cycle and pheromone-induced genes, and a morphologically-mixed inviable cell fate. Thus, specification and maintenance of a cellular state are performed by distinct interactions, which is likely a consequence of disparate reaction rates and may be a general feature of the interlinked regulatory networks responsible for selecting cell fates.

show abstract

“…Sic1 is targeted at multiple sites by several kinases such as Hog1 (Escote et al, 2004), Pho85 (Nishizawa et al, 1998), Ime2 (Sedgwick et al, 2006) and CK2 (Barberis et al, 2005b;Coccetti et al, 2006), but the effect of these phosphorylations on Sic1 stability is not fully understood. In addition, phosphorylations stabilizing Sic1 has been also reported, mediated by the phosphatase Cdc14 (Visintin et al, 1998) and Dcr2 (Pathak et al, 2007).…”

Section: Is Sic1 Part Of the Mechanism That Regulates Cell Cycle Coormentioning

confidence: 93%

Sic1 plays a role in timing and oscillatory behaviour of B-type cyclins

Barberis

Linke

Adrover

et al. 2012

Biotechnology Advances

View full text Add to dashboard Cite

Budding yeast cell cycle oscillates between states of low and high cyclin-dependent kinase activity, driven by association of Cdk1 with B-type (Clb) cyclins. Various Cdk1-Clb complexes are activated and inactivated in a fixed, temporally regulated sequence, inducing the behaviour known as "waves of cyclins". The transition from low to high Clb activity is triggered by degradation of Sic1, the inhibitor of Cdk1-Clb complexes, at the entry to S phase. The G(1) phase is characterized by low Clb activity and high Sic1 levels. High Clb activity and Sic1 proteolysis are found from the beginning of the S phase until the end of mitosis. The mechanism regulating the appearance on schedule of Cdk1-Clb complexes is currently unknown. Here, we analyse oscillations of Clbs, focusing on the role of their inhibitor Sic1. We compare mathematical networks differing in interactions that Sic1 may establish with Cdk1-Clb complexes. Our analysis suggests that the wave-like cyclins pattern derives from the binding of Sic1 to all Clb pairs rather than from Clb degradation. These predictions are experimentally validated, showing that Sic1 indeed interacts and coexists in time with Clbs. Intriguingly, a sic1Δ strain looses cell cycle-regulated periodicity of Clbs, which is observed in the wild type, whether a SIC1-0P strain delays the formation of Clb waves. Our results highlight an additional role for Sic1 in regulating Cdk1-Clb complexes, coordinating their appearance.

show abstract

The Dcr2p phosphatase destabilizes Sic1p in Saccharomyces cerevisiae

Cited by 9 publications

References 28 publications

The effective application of a discrete transition model to explore cell-cycle regulation in yeast

The effective application of a discrete transition model to explore cell-cycle regulation in yeast

Distinct Interactions Select and Maintain a Specific Cell Fate

Sic1 plays a role in timing and oscillatory behaviour of B-type cyclins

Contact Info

Product

Resources

About