IRIC - Institute for Research in Immunology and Cancer

Published on August 1, 2023

Massive dephosphorylation of numerous proteins is a major mechanism for the completion of cell division. The PP2A-B55 phosphatase is one of the players promoting mitosis exit, yet its direct targets have not been fully identified. IRIC’s Cell Cycle Regulation Research Unit and Proteomics and Mass Spectrometry Research Unit, headed respectively by Professors Vincent Archambault and Pierre Thibault, have taken advantage of the fruit fly Drosophila melanogaster to identify PP2A-B55 target proteins. Their results reveal that the nuclear envelope protein Emerin is dephosphorylated by PP2A-B55, a regulation event that is important for nuclear envelope reformation and embryonic development. Conducted jointly by doctoral students Virginie Emond-Fraser and Myreille Larouche, the study is published in the Royal Society‘s Open Biology journal.

PP2A-B55 binds and dephosphorylates Emerin

To identify the targets of the PP2A-B55 phosphatase during mitosis exit, two approaches were used. First, the team identified proteins that physically interact with PP2A-B55 in the fly embryo, at a developmental stage during which mitoses are frequent and rapid. In parallel, phosphoproteomics experiments identified potential targets whose phosphorylation levels depend on PP2A-B55 activity. Analysis of the two datasets identified Emerin, a nuclear envelope protein, as a likely target of PP2A-B55.

An important regulation for nuclear reformation and embryonic development

Using biochemical and microscopic approaches, the researchers observed that dephosphorylation of Emerin by PP2A-B55 enables it to form a complex with two other nuclear envelope proteins, forming a glue between DNA and nuclear membranes. Assembly of the complex thus promotes formation of the nuclear envelope around chromosomes that have been segregated during mitosis exit. Furthermore, genetic experiments revealed that Emerin phosphoregulation by PP2A-B55 is important in vivo: its alteration is lethal to developing embryos.

In sum, this study identified the nuclear envelope protein Emerin as being phosphoregulated by PP2A-B55 during mitosis exit, a mechanism that could be key to post-mitotic nuclear reformation in many species, including humans.

Cited study

Emond-Fraser V, Larouche M, Kubiniok P, Bonneil É, Li J, Bourouh M, Frizzi L, Thibault P, Archambault V. Identification of PP2A-B55 targets uncovers regulation of emerin during nuclear envelope reassembly in Drosophila. Open Biology. 2023 13:230104. https://doi.org/10.1098/rsob.230104