CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment.
The cytoplasmic linker protein (CLIP)-170, an outer kinetochore protein, has a role in kinetochore-microtubule attachment and chromosome alignment during mitosis. However, the mechanism by which CLIP-170 is involved in chromosome alignment is not known. Here, we show that CLIP-170 colocalizes with Polo-like kinase 1 (PLK1) at kinetochores during early mitosis. Depletion of CLIP-170 results in a significant reduction in PLK1 recruitment to kinetochores and causes kinetochore-fiber (K-fiber) instability and defects in chromosome alignment at the metaphase plate. These phenotypes are dependent on the phosphorylation of CLIP-170 at a CDK1-dependent site, T287, as ectopic expression of wild-type CLIP-170, but not the expression of a non-phosphorylatable mutant, CLIP-170-T287A, restores PLK1 localization at kinetochores and rescues K-fiber stability and chromosome alignment in CLIP-170-depleted cells. These data suggest that CLIP-170 acts as a novel recruiter and spatial regulator of PLK1 at kinetochores during early mitosis, promoting K-fiber stability and chromosome alignment for error-free chromosome segregation.
Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan mabmain@yahoo.com k.tanaka@idac.tohoku.ac.jp.
Mohammed Abdullahel
MA
Amin
Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.
Go
G
Itoh
Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.
Kenji
K
Iemura
Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.
Masanori
M
Ikeda
Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan mabmain@yahoo.com k.tanaka@idac.tohoku.ac.jp.
Kozo
K
Tanaka
D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C076744:cytoplasmic linker protein 170
CLIP-170; Chromosome alignment; Kinetochore; Kinetochore-fiber; PLK1