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CIP2A ModulatesCell-CycleProgression in HumanCancer Cells byRegulating theStability andActivity of Plk1 Jae‐Sung KimEun Ju KimJeong Su Oh2013 год

CIP2A Modulates Cell-Cycle Progression in Human Cancer Cells by Regulating the Stability and Activity of Plk1
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Аннотация: Abstract Abnormal cell-cycle control can lead to aberrant cell proliferation and cancer. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) is an inhibitor of protein phosphatase 2A (PP2A) that stabilizes c-Myc. However, the precise role of CIP2A in cell division is not understood. Herein, we show that CIP2A is required for mitotic progression by regulating the polo-like kinase (Plk1). With mitotic entry, CIP2A translocated from the cytoplasm to the nucleus, where it was enriched at spindle poles. CIP2A depletion delayed mitotic progression, resulting in mitotic abnormalities independent of PP2A activity. Unexpectedly, CIP2A interacted directly with the polo-box domain of Plk1 during mitosis. This interaction was required to maintain Plk1 stability by blocking APC/C-Cdh1–dependent proteolysis, thereby enhancing the kinase activity of Plk1 during mitosis. We observed strong correlation and in vivo interactions between these two proteins in multiple human cancer specimens. Overall, our results established a novel function for CIP2A in facilitating the stability and activity of the pivotal mitotic kinase Plk1 in cell-cycle progression and tumor development. Cancer Res; 73(22); 6667–78. ©2013 AACR.
Год издания: 2013
Авторы: Jae‐Sung Kim, Eun Ju Kim, Jeong Su Oh, In‐Chul Park, Sang‐Gu Hwang
Издательство: American Association for Cancer Research
Источник: Cancer Research
Ключевые слова: Microtubule and mitosis dynamics, Ubiquitin and proteasome pathways, Cancer-related Molecular Pathways
Другие ссылки: Cancer Research (HTML)
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