TTK kinase is essential for the centrosomal localization of TACC2
Abstract
Chromosome segregation in mitosis is orchestrated by dynamic interaction between spindle microtubule and the kinetochore. Our recent ultrastructural studies demonstrated a dynamic distribution of TTK, from the kinetochore to the centrosome, as cell enters into anaphase. Here, we show that a centrosomal protein TACC2 is phosphorylated in mitosis by TTK signaling pathway. TACC2 was pulled down by wild type TTK but not kinase death mutant, suggesting the potential phosphorylation-mediated interaction between these two proteins. Our immunofluorescence studies revealed that both TTK and TACC2 are located to the centrosome. Interestingly, expression of kinase death mutant of TTK eliminated the centrosomal localization of TACC2 but not other centrosomal proteins such as γ-tubulin and NuMA, a phenotype seen in TTK-depleted cells. In these centrosomal TACC2-liberated cells, chromosomes were lagging and mis-aligned. In addition, the distance between two centrosomes was markedly reduced, suggesting that centrosomal TACC2 is required for mitotic spindle maintenance. The inter-relationship between TTK and TACC2 established here provides new avenue to study centrosome and spindle dynamics underlying cell divisional control.
- Publication:
-
FEBS Letters
- Pub Date:
- August 2004
- DOI:
- 10.1016/j.febslet.2004.06.092
- Bibcode:
- 2004FEBSL.572...51D
- Keywords:
-
- Mitotic spindle;
- Kinetochore;
- Centrosome;
- TTK;
- TACC2;
- TACC;
- transforming acidic coiled-coil;
- SDS–PAGE;
- SDS–polyacrylamide gel electrophoresis;
- DAPI;
- 4;
- 6-diamidino-2-phenylindole