TTK kinase is essential for the centrosomal localization of TACC2.
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 gamma-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.
Hefei National Laboratory for Physical Sciences at Micro-scale, Hefei 230027, China.
Zhen
Z
Dou
Xia
X
Ding
Arzhang
A
Zereshki
Ying
Y
Zhang
Jie
J
Zhang
Feng
F
Wang
Jie
J
Sun
He
H
Huang
Xuebiao
X
Yao
D000705:Anaphase; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D018385:Centrosome / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D007700:Kinetics; D008938:Mitosis; D016296:Mutagenesis; D011494:Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000302:isolation & purification / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C410333:TACC2 protein, human; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human