Article Dans Une Revue Developmental Biology Année : 2025

Mitosis Localization Signal (MLS) extends KA1 and regulates MELK kinase localization to plasma membrane and activity in Xenopus embryo

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MELK is a cell-cycle dependent serine/threonine protein kinase whose expression is elevated in proliferating and cancer cells. In the Xenopus embryo, MELK overexpression induces cytokinesis failure, leading to multinucleated cells. This phenotype requires MELK catalytic activity, which correlates with MELK conformational modification and its localization to the cell membrane. How MELK activation and localization are coordinated remains unclear. Here, we show that in Xenopus gastrula epithelial cells MELK is abruptly enriched at the plasma membrane starting precisely from the metaphase-to-anaphase transition until early interphase. We show that deletion of the Kinase-Associated domain 1 (KA1), involved in binding to anionic phospholipids, does not abolish MELK localization to the plasma membrane. By a series of deletions, we identified a new 41-amino-acid domain, called Mitosis Localization Signal (MLS) that regulates MELK localization to the plasma membrane in dividing cells. We show that MLS cooperates with KA1 to regulate MELK localization and is necessary to induce cytokinesis failure when MELK is overexpressed. Our findings highlight the importance of MLS in MELK localization and in regulating MELK activity.

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hal-05232675 , version 1 (03-11-2025)

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Caroline Badouel, Guillaume Hatte, Claude Prigent, Jacek Kubiak, Jean-Pierre Tassan. Mitosis Localization Signal (MLS) extends KA1 and regulates MELK kinase localization to plasma membrane and activity in Xenopus embryo. Developmental Biology, 2025, 527, pp.206-217. ⟨10.1016/j.ydbio.2025.08.011⟩. ⟨hal-05232675⟩
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