Sic1 as a timer of Clb cyclin waves in the yeast cell cycle--design principle of not just an inhibitor

The FEBS Journal
Matteo Barberis

Abstract

Cellular systems biology aims to uncover design principles that describe the properties of biological networks through interaction of their components in space and time. The cell cycle is a complex system regulated by molecules that are integrated into functional modules to ensure genome integrity and faithful cell division. In budding yeast, cyclin-dependent kinases (Cdk1/Clb) drive cell cycle progression, being activated and inactivated in a precise temporal sequence. In this module, which we refer to as the 'Clb module', different Cdk1/Clb complexes are regulated to generate waves of Clb activity, a functional property of cell cycle control. The inhibitor Sic1 plays a critical role in the Clb module by binding to and blocking Cdk1/Clb activity, ultimately setting the timing of DNA replication and mitosis. Fifteen years of research subsequent to the identification of Sic1 have lead to the development of an integrative approach that addresses its role in regulating the Clb module. Sic1 is an intrinsically disordered protein and achieves its inhibitory function by cooperative binding, where different structural regions stretch on the Cdk1/Clb surface. Moreover, Sic1 promotes S phase entry, facilitating Cdk1/Clb5 nuclear transpo...Continue Reading

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Citations

Jul 16, 2013·Journal of Biotechnology·Adriana SupadyMatteo Barberis
May 9, 2015·Mass Spectrometry Reviews·Jinyu LiRita Grandori
Sep 12, 2015·Nature Communications·Marta Moreno-TorresClaudio De Virgilio
Oct 27, 2016·Scientific Reports·Kristelle Desfossés-BaronHugo Wurtele
Apr 1, 2017·International Journal of Molecular Sciences·Prakash Kulkarni, Vladimir N Uversky
Apr 5, 2020·NPJ Systems Biology and Applications·Thierry D G A MondeelMatteo Barberis
Jul 27, 2018·Computational and Mathematical Methods in Medicine·JungJun LeeJa-Yong Koo
May 13, 2017·Cell Discovery·Marta Moreno-TorresClaudio De Virgilio
Jun 27, 2017·NPJ Systems Biology and Applications·Christian LinkeMatteo Barberis
Jun 13, 2021·NPJ Systems Biology and Applications·Matteo Barberis

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