Cancerous inhibitor of protein phosphatase 2A (CIP2A) protein is involved in centrosome separation through the regulation of NIMA (never in mitosis gene A)-related kinase 2 (NEK2) protein activity.
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.
From the Research Center for Women's Disease, Department of Life Systems and.
Ae Lee
AL
Jeong
Sunyi
S
Lee
Jeong Su
JS
Park
Sora
S
Han
Chang-Young
CY
Jang
Jong-Seok
JS
Lim
Myung Sok
MS
Lee
Young
Y
Yang
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism*; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D016195:G2 Phase / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000072379:NIMA-Related Kinases; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020798:Two-Hybrid System Techniques
D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; C573112:KIAA1524 protein, mouse; D008565:Membrane Proteins; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; C490317:Nek2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2
CIP2A; Cell Cycle; Centrosome; Centrosome Separation; Mitosis; Mitotic Spindle; NEK2; PP2A