TY  - JOUR
TI  - The master Greatwall kinase, a critical regulator of mitosis and meiosis
AU  - Vigneron, Suzanne
AU  - Robert, Perle
AU  - Hached, Khaled
AU  - Sundermann, Lena
AU  - Charrasse, Sophie
AU  - Labbé, Jean-Claude
AU  - Castro, Anna
AU  - Lorca, Thierry
T2  - The International Journal of Developmental Biology
AB  - Entry into mitosis requires the coordinated activation of various protein kinases and phosphatases that together activate sequential signaling pathways allowing entry, progression and exit of mitosis. The limiting step is thought to be the activation of the mitotic Cdk1-cyclin B kinase. However, this model has recently evolved with new data showing that in addition to the Cdk1-cyclin B complex, Greatwall (Gwl) kinase is also required to enter into and maintain mitosis. This new concept proposes that entry into mitosis is now based on the combined activation of both kinases Cdk1-cyclin B and Gwl, the former promoting massive phosphorylation of mitotic substrates and the latter inhibiting PP2A-B55 phosphatase responsible for dephosphorylation of these substrates. Activated Gwl phosphorylates both Arpp19 and ENSA, which associate and inhibit PP2A-B55. This pathway seems relatively well conserved from yeast to humans, although some differences appear based on models or techniques used. While Gwl is activated by phosphorylation, its inactivation requires dephosphorylation of critical residues. Several phosphatases such as PP1, PP2A-B55 and FCP1 are required to control the dephosphorylation and inactivation of Gwl and a properly regulated mitotic exit. Gwl has also been reported to be involved in cancer processes and DNA damage recovery. These new findings support the idea that the Gwl-Arpp19/ENSA-PP2A-B55 pathway is essential to achieve an efficient division of cells and to maintain genomic stability.
PY  - 2016
DO  - 10.1387/ijdb.160155tl
VL  - 60
IS  - 7-8-9
SP  - 245
EP  - 254
J2  - Int. J. Dev. Biol.
LA  - en
SN  - 0214-6282
SN  - 1696-3547
UR  - https://ijdb.ehu.eus/article/160155tl
Y2  - 2024/11/21/18:04:39
ER  -