The Overlooked Greatwall: a New Perspective on Mitotic Control

Overview

Journal Open Biol

Specialties Biology
Cell Biology
Molecular Biology

Date 2012 Jul 4

PMID 22754657

Citations 42

Authors

David M Glover

Affiliations

Soon will be listed here.

Abstract

The role of the dual specificity protein phosphatase, Cdc25, in activating the cyclin-dependent kinase-cyclin B complex (Cdk1-CycB) by overcoming the inhibitory Wee1 kinase is a long-established principle for mitotic entry. Recently, however, evidence has emerged of a regulatory network that facilitates Cdk1-CycB activity by inhibiting the form of protein phosphatase 2A having a B55 regulatory subunit (PP2A-B55). Here, I review the genetic and biochemical evidence for Greatwall kinase and its substrate Endosulphine as the key components of this previously obscure regulatory network. Not only is the inhibition of PP2A-B55 by phospho-endosulphine required to prevent dephosphorylation of Cdk1-CycB substrates until mitotic exit, but it is also required to promote Cdc25 activity and inhibit Wee1 at mitotic entry. I discuss how these alternating states of preferential PP2A-B55 or Cdk1-CycB activity can have an impact upon the regulation of Polo kinase and its ability to bind different partner proteins as mitosis progresses.

Citing Articles

The MAST kinase KIN-4 carries out mitotic entry functions of Greatwall in C. elegans.

Roumbo L, Ossareh-Nazari B, Vigneron S, Stefani I, Van Hove L, Legros V EMBO J. 2025; .

PMID: 39962268 DOI: 10.1038/s44318-025-00364-w.

PP2A-B55 phosphatase counteracts Ki-67-dependent chromosome individualization during mitosis.

Sanz-Flores M, Ruiz-Torres M, Aguirre-Portoles C, El Bakkali A, Salvador-Barbero B, Villarroya-Beltri C Cell Rep. 2024; 43(7):114494.

PMID: 39003739 PMC: 11290319. DOI: 10.1016/j.celrep.2024.114494.

Eukaryotic cell size regulation and its implications for cellular function and dysfunction.

Chadha Y, Khurana A, Schmoller K Physiol Rev. 2024; 104(4):1679-1717.

PMID: 38900644 PMC: 11495193. DOI: 10.1152/physrev.00046.2023.

Greatwall-Endos-PP2A/B55 network regulates translation and stability of maternal transcripts in the oocyte-to-embryo transition.

Rangone H, Bond L, Weil T, Glover D Open Biol. 2024; 14(6):240065.

PMID: 38896085 PMC: 11286125. DOI: 10.1098/rsob.240065.

Programmed disassembly of a microtubule-based membrane protrusion network coordinates 3D epithelial morphogenesis in Drosophila.

Tran N, Montanari M, Gui J, Lubenets D, Fischbach L, Antson H EMBO J. 2024; 43(4):568-594.

PMID: 38263333 PMC: 10897427. DOI: 10.1038/s44318-023-00025-w.

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