Dario Segura Pena

• Segura Pena, Dario; Hovet, Oda; Gogoi, Hemanga; Dawicki-Mckenna, Jennine; Wøien, Stine Malene Hansen & Carrer, Manuel [Vis alle 9 forfattere av denne artikkelen] (2023). The structural basis of the multi-step allosteric activation of Aurora B kinase. eLIFE. ISSN 2050-084X. 12. doi: 10.7554/eLife.85328. Fulltekst i vitenarkiv Vis sammendrag

  Aurora B, together with IN-box, the C-terminal part of INCENP, forms an enzymatic complex that ensures faithful cell division. The [Aurora B/IN-box] complex is activated by autophosphorylation in the Aurora B activation loop and in IN-box, but it is not clear how these phosphorylations activate the enzyme. We used a combination of experimental and computational studies to investigate the effects of phosphorylation on the molecular dynamics and structure of [Aurora B/IN-box]. In addition, we generated partially phosphorylated intermediates to analyze the contribution of each phosphorylation independently. We found that the dynamics of Aurora and IN-box are interconnected, and IN-box plays both positive and negative regulatory roles depending on the phosphorylation status of the enzyme complex. Phosphorylation in the activation loop of Aurora B occurs intramolecularly and prepares the enzyme complex for activation, but two phosphorylated sites are synergistically responsible for full enzyme activity.

• Stonyte, Vilte; Martîn, Ruth Martîn; Segura-Pena, Dario; Sekulic, Nikolina & Lopez Aviles, Sandra (2020). Requirement of PP2A-B56 Par1 for the Stabilization of the CDK Inhibitor Rum1 and Activation of APC/C Ste9 during Pre-Start G1 in S. pombe. iScience. ISSN 2589-0042. 23(5). doi: 10.1016/j.isci.2020.101063. Fulltekst i vitenarkiv Vis sammendrag

  Exit from the cell cycle during the establishment of quiescence and upon cell differentiation requires the sustained inactivation of CDK complexes. Fission yeast cells deprived of nitrogen halt cell cycle progression in pre-Start G1, before becoming quiescent or undergoing sexual differentiation. The CDK inhibitor Rum1 and the APC/C activator Ste9 are fundamental for this arrest, but both are down-regulated by CDK complexes. Here, we show that PP2A-B56Par1 is instrumental for Rum1 stabilization and Ste9 activation. In the absence of PP2A-B56Par1, cells fail to accumulate Rum1, and this results in persistent CDK activity, Ste9 inactivation, retention of the mitotic cyclin Cdc13, and impaired withdrawal from the cell cycle during nitrogen starvation. Importantly, mutation of a putative B56 interacting motif in Rum1 recapitulates these defects. These results underscore the relevance of CDK-counteracting phosphatases in cell differentiation, establishment of the quiescent state, and escape from it in cancer cells.

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