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

Cell reports 2024 Jul 23

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Cell cycle progression is regulated by the orderly balance between kinase and phosphatase activities. PP2A phosphatase holoenzymes containing the B55 family of regulatory B subunits function as major CDK1-counteracting phosphatases during mitotic exit in mammals. However, the identification of the specific mitotic roles of these PP2A-B55 complexes has been hindered by the existence of multiple B55 isoforms. Here, through the generation of loss-of-function genetic mouse models for the two ubiquitous B55 isoforms (B55α and B55δ), we report that PP2A-B55α and PP2A-B55δ complexes display overlapping roles in controlling the dynamics of proper chromosome individualization and clustering during mitosis. In the absence of PP2A-B55 activity, mitotic cells display increased chromosome individualization in the presence of enhanced phosphorylation and perichromosomal loading of Ki-67. These data provide experimental evidence for a regulatory mechanism by which the balance between kinase and PP2A-B55 phosphatase activity controls the Ki-67-mediated spatial organization of the mass of chromosomes during mitosis. Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

María Sanz-Flores, Miguel Ruiz-Torres, Cristina Aguirre-Portolés, Aicha El Bakkali, Beatriz Salvador-Barberó, Carolina Villarroya-Beltri, Sagrario Ortega, Diego Megías, Daniel W Gerlich, Mónica Álvarez-Fernández, Marcos Malumbres. PP2A-B55 phosphatase counteracts Ki-67-dependent chromosome individualization during mitosis. Cell reports. 2024 Jul 23;43(7):114494