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J Cell Biol January 1, 2019; 218 (2): 541-558.

ENSA and ARPP19 differentially control cell cycle progression and development.

Hached K , Goguet P , Charrasse S , Vigneron S , Sacristan MP , Lorca T , Castro A .

Greatwall (GWL) is an essential kinase that indirectly controls PP2A-B55, the phosphatase counterbalancing cyclin B/CDK1 activity during mitosis. In Xenopus laevis egg extracts, GWL-mediated phosphorylation of overexpressed ARPP19 and ENSA turns them into potent PP2A-B55 inhibitors. It has been shown that the GWL/ENSA/PP2A-B55 axis contributes to the control of DNA replication, but little is known about the role of ARPP19 in cell division. By using conditional knockout mouse models, we investigated the specific roles of ARPP19 and ENSA in cell division. We found that Arpp19, but not Ensa, is essential for mouse embryogenesis. Moreover, Arpp19 ablation dramatically decreased mouse embryonic fibroblast (MEF) viability by perturbing the temporal pattern of protein dephosphorylation during mitotic progression, possibly by a drop of PP2A-B55 activity inhibition. We show that these alterations are not prevented by ENSA, which is still expressed in Arpp19Δ/Δ MEFs, suggesting that ARPP19 is essential for mitotic division. Strikingly, we demonstrate that unlike ARPP19, ENSA is not required for early embryonic development. Arpp19 knockout did not perturb the S phase, unlike Ensa gene ablation. We conclude that, during mouse embryogenesis, the Arpp19 and Ensa paralog genes display specific functions by differentially controlling cell cycle progression.

PubMed ID: 30626720
PMC ID: PMC6363464
Article link: J Cell Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: arpp19 bub1b ccnb1.2 cdk1 ensa epha8 h2bc21 isyna1 mastl mink1 prc1 ptpa ticrr

Article Images: [+] show captions
References [+] :
Abe, The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II. 2011, Pubmed