کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2107521 | 1083683 | 2010 | 13 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: SIK2 Is a Centrosome Kinase Required for Bipolar Mitotic Spindle Formation that Provides a Potential Target for Therapy in Ovarian Cancer SIK2 Is a Centrosome Kinase Required for Bipolar Mitotic Spindle Formation that Provides a Potential Target for Therapy in Ovarian Cancer](/preview/png/2107521.png)
SummaryRegulators of mitosis have been successfully targeted to enhance response to taxane chemotherapy. Here, we show that the salt inducible kinase 2 (SIK2) localizes at the centrosome, plays a key role in the initiation of mitosis, and regulates the localization of the centrosome linker protein, C-Nap1, through S2392 phosphorylation. Interference with the known SIK2 inhibitor PKA induced SIK2-dependent centrosome splitting in interphase while SIK2 depletion blocked centrosome separation in mitosis, sensitizing ovarian cancers to paclitaxel in culture and in xenografts. Depletion of SIK2 also delayed G1/S transition and reduced AKT phosphorylation. Higher expression of SIK2 significantly correlated with poor survival in patients with high-grade serous ovarian cancers. We believe these data identify SIK2 as a plausible target for therapy in ovarian cancers.
► A kinome screen identifies SIK2 as a centrosome kinase required for mitosis
► SIK2 phosphorylates C-Nap1 and is required for centrosome separation in mitosis
► Targeted SIK2 depletion results in synergy with taxanes in ovarian cancers
► Depletion of SIK2 results in delayed G1/S transition and low AKT phosphorylation
Journal: - Volume 18, Issue 2, 17 August 2010, Pages 109–121