Nilsson Group – University of Copenhagen

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Mitotic Mechanisms and Regulation 

The Mitotic Mechanisms and Regulation research group is headed by Jakob Nilsson.

First row from the left: Dimitriya Hristoforova Garvanska, Thomas Kruse, Jakob Nilsson, Jamin Hein, Gang Zhang, Emil Peter Thrane Hertz, Maria Sofie Yoo Larsen, Amanda Gammelby Qvesel

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 (Hertz et al 2016, Hein et al 2017).

Protein phosphatases have been viewed as unspecific enzymes that merely act to counteract the specific kinases but research in recent years have revealed that in fact protein phosphatases are tightly controlled and act precisely on specific substrates. A bottleneck in our understanding of protein phosphatases is to understand how they selectively target specific phosphorylation sites on specific proteins. An emerging theme from the study of a limited number of protein phosphatases is that they recognize short linear interaction motifs (SLiMs) in substrates and that these SLiMs provide specificity. SLiMs are often found in unstructured parts of proteins with 3 residues in a stretch of 10 amino acids conferring binding specificity. We recently described the first SLiM for a PP2A complex and showed how this confers specificity to PP2A-B56 (Hertz et al 2016). Interestingly this SLiM is used by the Ebola virus to highjack PP2A-B56 during viral infection (Kruse et al 2018).

PP2A-B56 recognizes substrates by binding to the LxxIxE motif and on the left a cell undergoing cell division with chromosomes in yellow and kinetochores in red.

To expand our 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.

In addition we focus on understanding the role of the kinetochore in ensuring accurate chromosome segregation during mitosis. We are particularly interested in understanding how unattached kinetochores catalyze a “wait anaphase” signal by recruiting and activating checkpoint proteins (Zhang et al 2017, 2016, 2015). The recruitment of the checkpoint proteins is tightly controlled through phosphorylations and therefore understanding the opposing protein phosphatases is also the focus of our studies.

We are always looking for highly motivated master students, PhDs or Post Doc so please fell free to contact us. For more information and inquiries about available positions please contact Prof. Jakob Nilsson (jakob.nilsson@cpr.ku.dk).

Selected recent publications:

Kruse T, Biedenkopf N, Hertz EPT, Dietzel E, Stalmann G, Lopez-Mendez B, Davey NE, Nilsson J, Becker S. (2018)
The Ebola virus nucleoprotein recruits the host PP2A-B56 phosphatase to activate transcriptional support activity of VP30 Molecular Cell. 69(1): 136-145
Shared corresponding author.

Hein JB, Hertz EPT, Garvanska DH, Kruse T, Nilsson J (2017)
Distinct kinetics of serine and threonine dephosphorylation is essential for mitosis
Nature Cell Biology, 19(12): 1433-1440

Zhang G, Kruse T, Lopez-Mendez B, Sylvestersen KB, Garvanska DH, Schopper S, Nielsen ML, Nilsson J (2017)
Bub1 positions Mad1 close to KNL1 MELT repeats to promote chcekpoint signalling
Nature Communications 8:15822 (2017)

Hertz EP, Kruse T, Davey NE, Lopez BL, Sigurdsson JO, Montoya G, Olsen JV, Nilsson J (2016)
A conserved motif provides binding specificity to the PP2A-B56 phosphatase
Molecular Cell 63(4): 686-95.
Paper highlighted by Nature Reviews Molecular Cell Biology

Zhang G, Mendez BL, Sedgwick GG, Nilsson J (2016)
Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation
Nature Communications 7:12256.

Hein JB & Nilsson J (2016)
Interphase APC/C-Cdc20 inhibition by cylin A2-Cdk2 ensures efficient mitotic entry
Nature Communications 7:10975.

Zhang G, Lischetti T, Hayward D, Nilsson J (2015)
Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint.
Nature Communications, 6: 7162.

Lischetti T, Zhang G, Sedgwick GG, Bolanos-Garcia V, Nilsson J (2014)
The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signaling and silencing.
Nature Communications, 5:5563.

Kruse T, Larsen MS, Sedgwick GG, Sigurdsson JO, Streicher W, Olsen JV, Nilsson J (2014)
A direct role of Mad1 in the spindle assembly checkpoint beyond kinetochore recruitment of Mad2
EMBO reports 15: 282-90.
Paper highlighted by hot off the press in EMBO reports

Hein JB & Nilsson J (2014)
Stable MCC binding to the APC/C is required for a functional spindle assembly checkpoint
EMBO reports 15: 264-72.