MPS1 kinase regulation by PP2A-B56 is vital for successful mitosis

MPS1 kinase regulation by PP2A-B56 is vital for successful mitosis

The ultimate goal of mitosis is to produce two daughter cells with the same genetic make-up as the parent cell. It consists of several steps, kept in check by proteins such as kinases and phosphates and deregulation of which is associated with human pathologies such as cancer.

One important kinase in this process is Mono-Polar Spindle 1 (MPS1), which monitors the correct formation of microtubule-kinetochore attachments and initiates spindle assembly checkpoint signalling in case of errors. MPS1 is also actively involved in resolving incorrect kinetochore attachments by phosphorylating outer kinetochore proteins. Accurate regulation of MPS1 kinase activity, via autophosphorylation of the MPS1 T-loop, is therefore critical for faithful chromosome segregation.

Hayward and colleagues from the Gruneberg lab have now shown that a kinetochore-associated pool of the PP2A-B56 phosphatase regulates the T-loop autophosphorylation of MPS1 and hence its kinase activity. Expression of a constitutively active form of MPS1 refractory to PP2A-B56 dephosphorylation results in exaggerated MPS1-mediated error correction, mitotic delays and impaired cell cycle progression, stressing the importance of balanced kinase and phosphatase activities for successful mitosis.

Iqbal Dulloo

Hayward D, Bancroft J, Mangat D, Alfonso-Pérez T, Dugdale S, McCarthy J, Barr FA, Gruneberg U. (2019)