Abstract
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is overexpressed in most human cancers and has been described as being involved in the progression of several human malignancies via the inhibition of protein phosphatase 2A (PP2A) activity toward c-Myc. However, with the exception of this role, the cellular function of CIP2A remains poorly understood. On the basis of yeast two-hybrid and coimmunoprecipitation assays, we demonstrate here that NIMA (never in mitosis gene A)-related kinase 2 (NEK2) is a binding partner for CIP2A. CIP2A exhibited dynamic changes in distribution, including the cytoplasm and centrosome, depending on the cell cycle stage. When CIP2A was depleted, centrosome separation and the mitotic spindle dynamics were impaired, resulting in the activation of spindle assembly checkpoint signaling and, ultimately, extension of the cell division time. Our data imply that CIP2A strongly interacts with NEK2 during G2/M phase, thereby enhancing NEK2 kinase activity to facilitate centrosome separation in a PP1- and PP2A-independent manner. In conclusion, CIP2A is involved in cell cycle progression through centrosome separation and mitotic spindle dynamics.
Highlights
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is overexpressed in most types of human cancer
CIP2A Localizes to Various Sites during the Cell Cycle— CIP2A is overexpressed in almost all types of human cancer and is known to inhibit phosphatase 2A (PP2A) activity toward c-Myc, the cellular function of CIP2A is poorly understood
CIP2A was mainly localized in the cytosol, a weak signal was observed in the nucleus at S phase and exhibited a multiplefocus shape in cells blocked at mitosis by nocodazole treatment (Fig. 1A)
Summary
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is overexpressed in most types of human cancer. Results: Depletion of CIP2A prolongs cell division time and CIP2A interacts with NIMA-related kinase 2 (NEK2) during G2/M phase to facilitate centrosome separation. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is overexpressed in most human cancers and has been described as being involved in the progression of several human malignancies via the inhibition of protein phosphatase 2A (PP2A) activity toward c-Myc. with the exception of this role, the cellular function of CIP2A remains poorly understood. CIP2A is involved in cell cycle progression through centrosome separation and mitotic spindle dynamics. CIP2A is known to cause c-Myc stabilization and is overexpressed in almost all human cancer types, with the exception of inhibiting PP2A activity toward c-Myc, the cellular function of CIP2A is poorly understood. In addition to the role in centrosome separation, NEK2 is known to be involved in meiotic events, including chromosomal condensation and segregation [42, 43], in microtubule stabilization through NIP2/centrobin [44, 45], and in kin-
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