PuSH - Publication Server of Helmholtz Zentrum München: The Aurora B-controlled PP1/RepoMan complex determines the spatial and temporal distribution of mitotic H2B S6 phosphorylation.

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Pfisterer, M.* ; Robert, R.* ; Saul, V.V.* ; Pritz, A.* ; Seibert, M.* ; Feederle, R. ; Schmitz, M.L.*

The Aurora B-controlled PP1/RepoMan complex determines the spatial and temporal distribution of mitotic H2B S6 phosphorylation.

Open Biol. 14:230460 (2024)

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	Open Access Gold

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The precise spatial and temporal control of histone phosphorylations is important for the ordered progression through the different phases of mitosis. The phosphorylation of H2B at S6 (H2B S6ph), which is crucial for chromosome segregation, reaches its maximum level during metaphase and is limited to the inner centromere. We discovered that the temporal and spatial regulation of this modification, as well as its intensity, are governed by the scaffold protein RepoMan and its associated catalytically active phosphatases, PP1α and PP1γ. Phosphatase activity is inhibited at the area of maximal H2B S6 phosphorylation at the inner centromere by site-specific Aurora B-mediated inactivation of the PP1/RepoMan complex. The motor protein Mklp2 contributes to the relocalization of Aurora B from chromatin to the mitotic spindle during anaphase, thus alleviating Aurora B-dependent repression of the PP1/RepoMan complex and enabling dephosphorylation of H2B S6. Accordingly, dysregulation of Mklp2 levels, as commonly observed in tumour cells, leads to the lack of H2B S6 dephosphorylation during early anaphase, which might contribute to chromosomal instability.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Centromere ; Histone Phosphorylation ; Mitosis ; Phosphatase Scaffold; Chromosomal Passenger Complex; Histone H3; Kinase; Survivin; Requires; Spindle; Mitosis; Dephosphorylation; Segregation; Instability

e-ISSN 2046-2441

Journal Open Biology

Quellenangaben Volume: 14, Issue: 5, Article Number: 230460

Publisher Royal Society of London

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Monoclonal Antibodies (CF-MAB)

Grants
Deutsche Forschungsgemeinschast (DFG, German Research Foundation)