CKAP2 phosphorylation by CDK1/cyclinB1 is crucial for maintaining centrosome integrity

• Published in: Experimental & molecular medicine 2017-07, Vol.49 (7), p.e354-e354
• Main Authors: Yoo, Bum Ho, Kang, Du-Seock, Park, Chi-Hu, Kang, Kyeongjin, Bae, Chang-Dae
• Format: Article
• Language: English
• Subjects: 14/19; 14/34; 38/109; 631/80/128/1965; 631/80/641; 82/58; Animals; Biomedical and Life Sciences; Biomedicine; CDC2 Protein Kinase - metabolism; Cell Cycle; Centrosome - metabolism; Centrosomes; Chromosome Segregation; Cyclin B - metabolism; Cyclin B1; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; DNA, Complementary - genetics; Ectopic expression; HEK293 Cells; Hepatocytes; Humans; Kinases; Medical Biochemistry; Mice; Mitosis; Molecular Medicine; Mutation; NIH 3T3 Cells; Original; original-article; Phosphorylation; Stem Cells
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/emm.2017.92

Previously, we have reported that CKAP2 is involved in the maintenance of centrosome integrity, thus allowing for proper mitosis in primary hepatocytes. To understand this biological process, we identified the mitosis-specific phosphorylation sites in mouse CKAP2 and investigated CKAP’s possible role in cell cycle progression. Because we observed mouse CKAP2 depletion in amplified centrosomes and aberrant chromosomal segregation, which was rescued by ectopic expression of wild-type CKAP2, we focused on the centrosome duplication process among the various aspects of the cell cycle. Among the identified phosphorylation sites, T603 and possibly S608 were phosphorylated by CDK1–cyclin B1 during mitosis, and the ectopic expression of both T603A and S608A mutants was unable to restore the centrosomal abnormalities in CKAP2-depleted cells. These results indicated that the phosphorylation status of CKAP2 during mitosis is critical for controlling both centrosome biogenesis and bipolar spindle formation. Cell division: Keeping it equal The cell-division protein CKAP2 must be tagged with phosphate groups (phosphorylated) at certain sites for cells to divide appropriately. During cell division, equal sharing of genetic material between the two resulting ‘daughter’ cells is crucial. Centrosomes are a key part of the complex web of filaments that perfectly divides the genetic material. Centrosomes must duplicate only once per cell division; extra centrosomes are a hallmark of cancer. CKAP2 was known to be involved in centrosome duplication, but its precise role remained unknown. Chang-Dae Bae at Sungkyunkwan University in Korea and coworkers identified potential CKAP2 phosphorylation sites, then made the sites untaggable. When CKAP2 was completely untagged, 30% of cells developed multiple centrosomes and divided improperly. The researchers identified two crucial phosphorylation sites. These results will help to identify targets for development of anticancer medications.