Journal
EMBO JOURNAL
Volume 29, Issue 17, Pages 2953-2965Publisher
WILEY
DOI: 10.1038/emboj.2010.174
Keywords
kinetochore; microtubule attachment; phosphorylation
Categories
Funding
- National Cancer Institute [K01 CA114401]
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CLIP-170 is implicated in the formation of kinetochore-microtubule attachments through direct interaction with the dynein/dynactin complex. However, whether this important function of CLIP-170 is regulated by phosphorylation is unknown. Herein, we have identified polo-like kinase 1 (Plk1) and casein kinase 2 (CK2) as two kinases of CLIP-170 and mapped S195 and S1318 as their respective phosphorylation sites. We showed that a CK2 unphosphorylatable mutant lost its ability to bind to dynactin and to localize to kinetochores during prometaphase, indicating that the CK2 phosphorylation of CLIP-170 is involved in its dynactin-mediated kinetochore localization. Furthermore, we provide evidence that Plk1 phosphorylation of CLIP-170 at S195 enhances its association with CK2. Finally, we detected defects in the formation of kinetochore fibres in cells expressing the CLIP-S195A and -S1318A, but not the CLIP-S195E and -S1318D, confirming that Plk1-and CK2-associated phosphorylations of CLIP-170 are involved in the timely formation of kinetochore-microtubule attachments in mitosis. The EMBO Journal (2010) 29, 2953-2965. doi: 10.1038/emboj.2010.174; Published online 27 July 2010
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