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Phosphoprocessors SIGNED

Biological signal processing via multisite phosphorylation networks

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EC-Contrib. €

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Project "Phosphoprocessors" data sheet

The following table provides information about the project.

Coordinator
TARTU ULIKOOL 

Organization address
address: ULIKOOLI 18
city: TARTU
postcode: 51005
website: www.ut.ee

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Estonia [EE]
 Project website http://www.looglab.com
 Total cost 1˙999˙288 €
 EC max contribution 1˙999˙288 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-05-01   to  2020-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    TARTU ULIKOOL EE (TARTU) coordinator 1˙999˙288.00

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 Project objective

Multisite phosphorylation of proteins is a powerful signal processing mechanism playing crucial roles in cell division and differentiation as well as in disease. Our goal in this application is to elucidate the molecular basis of this important mechanism. We recently demonstrated a novel phenomenon of multisite phosphorylation in cell cycle regulation. We showed that cyclin-dependent kinase (CDK)-dependent multisite phosphorylation of a crucial substrate is performed semiprocessively in the N-to-C terminal direction along the disordered protein. The process is controlled by key parameters including the distance between phosphorylation sites, the distribution of serines and threonines in sites, and the position of docking motifs. According to our model, linear patterns of phosphorylation networks along the disordered protein segments determine the net phosphorylation rate of the protein. This concept provides a new interpretation of CDK signal processing, and it can explain how the temporal order of cell cycle events is achieved. The goals of this study are: 1) We will seek proof of the model by rewiring the patterns of budding yeast Cdk1 multisite networks according to the rules we have identified, so to change the order of cell cycle events. Next, we will restore the order by alternative wiring of the same switches; 2) To apply the proposed model in the context of different kinases and complex substrate arrangements, we will study the Cdk1-dependent multisite phosphorylation of kinetochore components, to understand the phospho-regulation of kinetochore formation, microtubule attachment and error correction; 3) We will apply multisite phosphorylation to design circuits for synthetic biology. A toolbox of synthetic parts based on multisite phosphorylation would revolutionize the field since the fast time scales and wide combinatorial possibilities.

 Publications

year authors and title journal last update
List of publications.
2017 Alina Goldstein, Nurit Siegler, Darya Goldman, Haim Judah, Ervin Valk, Mardo Kõivomägi, Mart Loog, Larisa Gheber
Three Cdk1 sites in the kinesin-5 Cin8 catalytic domain coordinate motor localization and activity during anaphase
published pages: 3395-3412, ISSN: 1420-682X, DOI: 10.1007/s00018-017-2523-z
Cellular and Molecular Life Sciences 74/18 2020-04-23
2019 Mihkel Örd, Kaidi Möll, Alissa Agerova, Rait Kivi, Ilona Faustova, Rainis Venta, Ervin Valk, Mart Loog
Multisite phosphorylation code of CDK
published pages: 649-658, ISSN: 1545-9993, DOI: 10.1038/s41594-019-0256-4
Nature Structural & Molecular Biology 26/7 2020-04-23
2017 Christian Linke, Anastasia Chasapi, Alberto González-Novo, Istabrak Al Sawad, Silvia Tognetti, Edda Klipp, Mart Loog, Sylvia Krobitsch, Francesc Posas, Ioannis Xenarios, Matteo Barberis
A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle
published pages: , ISSN: 2056-7189, DOI: 10.1038/s41540-017-0008-1
npj Systems Biology and Applications 3/1 2020-04-23
2019 Mihkel Örd, Rainis Venta, Kaidi Möll, Ervin Valk, Mart Loog
Cyclin-Specific Docking Mechanisms Reveal the Complexity of M-CDK Function in the Cell Cycle
published pages: 76-89.e3, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.04.026
Molecular Cell 75/1 2020-04-23
2019 Alina Goldstein, Darya Goldman, Ervin Valk, Mart Loog, Liam J. Holt, Larisa Gheber
Synthetic-Evolution Reveals Narrow Paths to Regulation of the Saccharomyces cerevisiae Mitotic Kinesin-5 Cin8
published pages: 1125-1138, ISSN: 1449-2288, DOI: 10.7150/ijbs.30543
International Journal of Biological Sciences 15/6 2020-04-23
2019 Mihkel Örd, Mart Loog
How the cell cycle clock ticks
published pages: 169-172, ISSN: 1059-1524, DOI: 10.1091/mbc.e18-05-0272
Molecular Biology of the Cell 30/2 2020-04-23
2016 Jakobson L, Vaahtera L, Tõldsepp K, Nuhkat M, Wang C, Wang YS, Hõrak H, Valk E, Pechter P, Sindarovska Y, Tang J, Xiao C, Xu Y, Gerst Talas U, García-Sosa AT, Kangasjärvi S, Maran U, Remm M, Roelfsema MR, Hu H, Kangasjärvi J, Loog M, Schroeder JI, Kollist H, Brosché M.
Natural Variation in Arabidopsis Cvi-0 Accession Reveals an Important Role of MPK12 in Guard Cell CO2 Signaling.
published pages: , ISSN: 1544-9173, DOI:
Plos Biology 2020-04-23
2015 Doncic A, Atay O, Valk E, Grande A, Bush A, Vasen G, Colman-Lerner A, Loog M, Skotheim JM.
Compartmentalization of a bistable switch enables memory to cross a feedback-driven transition.
published pages: , ISSN: 0092-8674, DOI:
Cell 2020-04-23
2016 Hõrak H, Sierla M, Tõldsepp K, Wang C, Wang YS, Nuhkat M, Valk E, Pechter P, Merilo E, Salojärvi J, Overmyer K, Loog M, Brosché M, Schroeder JI, Kangasjärvi J, Kollist H.
A Dominant Mutation in the HT1 Kinase Uncovers Roles of MAP Kinases and GHR1 in CO2-Induced Stomatal Closure.
published pages: , ISSN: 1040-4651, DOI:
Plant Cell 2020-04-23
2015 Bhaduri S, Valk E, Winters MJ, Gruessner B, Loog M, Pryciak PM.
A Docking Interface in the Cyclin Cln2 Promotes Multi-site Phosphorylation of Substrates and Timely Cell-Cycle Entry
published pages: , ISSN: 0960-9822, DOI:
Current Biology 2020-04-23

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