TY  - JOUR
A1  - Raab, Monika
A1  - Matthess, Yves
A1  - Raab, Christopher A.
A1  - Gutfreund, Niklas
A1  - Dötsch, Volker
A1  - Becker, Sven
A1  - Sanhaji, Mourad
A1  - Strebhardt, Klaus
T1  - A dimerization-dependent mechanism regulates enzymatic activation and nuclear entry of PLK1
T2  - Oncogene
N2  - Polo-like kinase 1 (PLK1) is a crucial regulator of cell cycle progression. It is established that the activation of PLK1 depends on the coordinated action of Aurora-A and Bora. Nevertheless, very little is known about the spatiotemporal regulation of PLK1 during G2, specifically, the mechanisms that keep cytoplasmic PLK1 inactive until shortly before mitosis onset. Here, we describe PLK1 dimerization as a new mechanism that controls PLK1 activation. During the early G2 phase, Bora supports transient PLK1 dimerization, thus fine-tuning the timely regulated activation of PLK1 and modulating its nuclear entry. At late G2, the phosphorylation of T210 by Aurora-A triggers dimer dissociation and generates active PLK1 monomers that support entry into mitosis. Interfering with this critical PLK1 dimer/monomer switch prevents the association of PLK1 with importins, limiting its nuclear shuttling, and causes nuclear PLK1 mislocalization during the G2-M transition. Our results suggest a novel conformational space for the design of a new generation of PLK1 inhibitors.
KW  - Cell division
KW  - Mitosis
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/69573
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-695736
SN  - 1476-5594
N1  - This work was supported by grants from the Sander Stiftung (Nr. 2021.023.1), Deutsche Krebshilfe (70114007), German Cancer Consortium (DKTK), Heidelberg. Open Access funding enabled and organized by Projekt DEAL.
VL  - 41
SP  - 372
EP  - 386
PB  - Springer Nature
CY  - London
ER  -