Phosphorylation of CLIP-170 by Plk1 and CK2 promotes timely formation of kinetochore-microtubule attachments

Hongchang Li, X. Shawn Liu, Xiaoming Yang, Yingmin Wang, Yun Wang, Jerrold R. Turner, Xiaoqi Liu

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2953-2965
Number of pages13
JournalEMBO Journal
Volume29
Issue number17
DOIs
StatePublished - Sep 1 2010

Funding

FundersFunder number
National Childhood Cancer Registry – National Cancer InstituteK01CA114401
National Childhood Cancer Registry – National Cancer Institute

    Keywords

    • kinetochore
    • microtubule attachment
    • phosphorylation

    ASJC Scopus subject areas

    • General Neuroscience
    • Molecular Biology
    • General Biochemistry, Genetics and Molecular Biology
    • General Immunology and Microbiology

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