Mart Loog

Biological signal processing via multisite phosphorylation networks

Biological signal processing via protein phosphorylation plays a vital role in the functioning of living organisms, particularly in crucial processes like cell division and disease mechanisms that affect the organism. Therefore, gaining a deeper understanding of and enhancing control over this phenomenon hold immense significance for the future of the relevant sectors and industries. The Phosphoprocessors project aimed to build upon its team members’ previous research on multi-site phosphorylation and delve further into the intricate workings of cyclin-dependent kinases (CDK), the master regulators of cell division. By conducting rigorous testing, the ultimate goal was to attain a more comprehensive and explainable understanding of how multisite phosphorylation networks control cell cycle events.

Result

A series of discoveries by the project team has shifted the paradigm of how we understand cell cycle regulation and provided a mechanistic explanation for the quantitative model of cyclin-dependent kinase (CDK) function. CDK substrate recognition specificity and multisite phosphorylation mechanisms have explained how different CDK thresholds are encoded into CDK target proteins. The phosphorylation patterns act as barcodes, assigning each target phosphorylation to a specific time point during the cell cycle progression. These rules of encoding patterns of phosphorylation sites and cyclin docking sites along the disordered regions of CDK targets have opened an entirely new and hitherto unknown level of complexity for cell cycle regulation. It has led to a unified model for CDK-dependent ordering of cell cycle events, in which the quantitative model, multisite phosphorylation codes, and cyclin specificity work together to order cell cycle events.

Impact

The cell division cycle is the basic mechanism of life: all living things originate from a single cell, and the development of each organism begins with a single cell. The cell cycle is a complex process that requires systems and mechanisms that guarantee the assembly of a flawless copy of the cell. The study of the mechanisms regulating the cell cycle is important, most prominently for understanding cancers, which represent defective states of cell cycle control mechanisms leading to uncontrolled cell proliferation. We also need to know the mechanisms of cell cycle in the context of industrial biotechnology, for example, to optimize the growth and productivity of microbial biomass in bioreactors.