Mitotic mechanisms and regulation in the Nilsson Group

The Nilsson lab has two main focus areas; firstly how do protein phosphatases selectively recognize their substrates and secondly how are genome integrity maintained during cell division. These two topics are tightly connected as protein phosphatases are major regulators of cell division and therefore we often use cell division to illustrate fundamental principles of protein phosphatases selectivity.

Research focus

Protein phosphatases have been viewed as unspecific enzymes that merely act to counteract the specific kinases, but research in recent years has revealed that protein phosphatases are in fact tightly controlled and act precisely on specific substrates.

”Our aim is to bring the study of protein phosphatases from the realm of passive observation to a situation where precise engineering of signaling pathways is possible,” says Professor and Group Leader Jakob Nilsson.

A bottleneck in the understanding of protein phosphatases is to explore how they selectively target specific phosphorylation sites on specific proteins. The group recently described the first consensus motif for a PP2A complex and showed how this confers substrate specificity to PP2A-B56.

To expand the understanding of substrate selectivity by protein phosphatases the Nilsson lab is aiming to identify and characterize novel SLiMs for additional protein phosphatases and use this to precisely dissect phosphatase function in genome integrity pathways. This requires a multidisciplinary approach spanning biochemistry to cell biology.

Main findings

A conserved motif provides binding specificity to the PP2A-B56 phosphatase
We identify the LxxIxE motif as a general binding motif for PP2A-B56 and use this to dissect the function of PP2A-B56 in cytokinesis and transcriptional responses. This work is the first to describe a general principle for PP2A specificity and provides system-wide information on its function. 

Distinct kinetics of serine and threonine dephosphorylation is essential for mitosis”
We provide the first biological evidence to show that the inherent phosphothreonine preference for PP2A is important. This preference is used to control temporal timing of mitotic events. 

"The Ebola virus nucleoprotein recruits the host PP2A-B56 phosphatase to activate transcriptional support activity of VP30"
We identify PP2A-B56 as a novel host factor for the Ebola virus and mechanistically dissect the role of the phosphatase in viral infection. We furthermore validate PP2A-B56 as a therapeutic target for inhibition of Ebola infection.

Staff of the Nilsson Group

Group Leader: Professor Jakob Nilsson

Top row: Gang Zhang, Thomas Kruse, Sara Ambjørn
Bottom row: Yumi Ueki, Dimitriya Garvanska, Jakob Nilsson