Oda Hovet

• Hovet, Oda; Nahali, Negar; Halaburkova, Andrea; Haugen, Linda Hofstad; Paulsen, Jonas & Progida, Cinzia Anita Maria (2025). Nuclear mechano-confinement induces geometry-dependent HP1α condensate alterations. Communications Biology. 8. doi: 10.1038/s42003-025-07732-6. Full text in Research Archive Show summary

  Cells sense external physical cues through complex processes involving signaling pathways, cytoskeletal dynamics, and transcriptional regulation to coordinate a cellular response. A key emerging principle underlying such mechanoresponses is the interplay between nuclear morphology, chromatin organization, and the dynamic behavior of nuclear bodies such as HP1α condensates. Here, applying Airyscan super-resolution live cell imaging, we report a hitherto undescribed level of mechanoresponse triggered by cell confinement below their resting nuclear diameter, which elicits changes in the number, size and dynamics of HP1α nuclear condensates. Utilizing biophysical polymer models, we observe radial redistribution of HP1α condensates within the nucleus, influenced by changes in nuclear geometry. These insights shed new light on the complex relationship between external forces and changes in nuclear shape and chromatin organization in cell mechanoreception.

• Pena, Dario Segura; Hovet, Oda; Gogoi, Hemanga; Dawicki-Mckenna, Jennine; Wøien, Stine Malene Hansen & Carrer, Manuel [Show all 9 contributors for this article] (2023). The structural basis of the multi-step allosteric activation of Aurora B kinase. eLIFE. 12. doi: 10.7554/eLife.85328. Full text in Research Archive Show summary

  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.

• Sekulic, Nikolina; Hovet, Oda; Gogoi, Hemanga; Dawicki-McKenna, Jennine; Wøien, Stine Malene Hansen & Carrer, Manuel [Show all 8 contributors for this article] (2022). The structural basis of the multi-step allosteric activation of Aurora B kinase. BioRxiv. ISSN 0362-4331. Full text in Research Archive

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• Paulsen, Jonas & Hovet, Oda (2024). Cell nuclei deformation impacts heterochromatin condensate structures in human cell lines. Full text in Research Archive
• Hovet, Oda & Paulsen, Jonas (2023). Investigating nuclear deformation and the role of HP1alpha upon confinement. Full text in Research Archive
• Sekulic, Nikolina; Segura-Pena, Dario; Hovet, Oda; Dawicki-McKenna, Jennine; Wøien, Stine Malene Hansen & Black, Ben E. [Show all 7 contributors for this article] (2022). Aurora B activation requires synchronized internal motion initiated by IN-box phosphorylation. Full text in Research Archive
• Segura-Pena, Dario; Hovet, Oda; Dawicki-McKenna, Jennine; Wøien, Stine Malene Hansen; Black, Ben E. & Cascella, Michele [Show all 7 contributors for this article] (2022). The structural basis of the multi-step allosteric activation of Aurora B kinase. Full text in Research Archive
• Segura-Pena, Dario; Hovet, Oda; Dawicki-McKenna, Jennine; Wøien, Stine Malene Hansen; Black, Ben E. & Cascella, Michele [Show all 7 contributors for this article] (2022). HDX and MD as tools to elucidate Aurora B kinase activation mechanism. Full text in Research Archive
• Segura-Pena, Dario; Hovet, Oda; Dawicki-McKenna, Jennine; Wøien, Stine Malene Hansen; Black, Ben E. & Cascella, Michele [Show all 7 contributors for this article] (2022). Phosphorylation structurally organizes the [Aurora B/IN-box] complex and introduces a synchronised internal motion of the enzyme resulting in activation. Full text in Research Archive
• Segura-Pena, Dario; Hovet, Oda; Dawicki-McKenna, Jennine; Wøien, Stine Malene Hansen; Black, Ben E. & Cascella, Michele [Show all 7 contributors for this article] (2022). The structural basis of the multi-step allosteric activation of Aurora B kinase. Full text in Research Archive
• Segura-Pena, Dario; Hovet, Oda; Dawicki-McKenna, Jennine; Wøien, Stine Malene Hansen; Black, Ben E. & Cascella, Michele [Show all 7 contributors for this article] (2022). The structural basis of the multi-step allosteric activation of Aurora B kinase. Full text in Research Archive
• Sekulic, Nikolina; Cascella, Michele & Hovet, Oda (2020). Molecular Dynamics Studies on the Essential Mitotic Protein Kinase – Aurora B. Universitetet i Oslo. Full text in Research Archive Show summary

  Aurora B is a serine/threonine protein kinase. Its enzymatic activity is required for accurate chromosome segregation, spindle midzone stability and cell division. Aurora B kinase is always in association with the activator protein, INCENP, and full activity requires auto-phosphorylation of both, a threonine in the activation loop of Aurora B and the serines in the TSS-motif (Threonine-Serine-Serine) present on INCENP. Structural studies have revealed profound conformational changes in the enzyme complex upon auto-phosphorylation and initial hydrogen- deuterium exchange studies indicate structural dynamic changes associated with auto-phosphorylation. In this study, we have used molecular dynamics to simulate three phosphorylation states of the enzyme complex (non-phosphorylated enzyme complex, enzyme complex phosphorylated only in the activation loop of Aurora B and enzyme complex phosphorylated in both loop of Aurora B and INCENP). We found that phosphorylation has a profound impact on the structure and dynamics of Aurora B/INCENP-complex inducing allosteric communication between INCENP and Aurora B. Upon phosphorylation of the threonine in the activation loop of Aurora B, INCENP adopts a dramatic conformational change and comes into close contact with the activation loop region. Other analyzed regions undergoing noticeable structural changes upon phosphorylation are the active site where ATP becomes more stably bound, the activation loop that becomes more rigid and the αG-helix experiencing a shift towards the core of Aurora B. Principle component analysis revealed a synchronized motion in the fully phosphorylated state of the enzyme complex with coupled open-close and activation loop motions, a feature that might contribute to increased activity. The insights into regulation of Aurora B/INCENP-complex provided in our study might help towards generating a more specific inhibitor of Aurora B in future cancer treatment.

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