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J Cell Biol April 11, 2005; 169 (1): 49-60.

ZW10 links mitotic checkpoint signaling to the structural kinetochore.

Kops GJ , Kim Y , Weaver BA , Mao Y , McLeod I , Yates JR , Tagaya M , Cleveland DW .

The mitotic checkpoint ensures that chromosomes are divided equally between daughter cells and is a primary mechanism preventing the chromosome instability often seen in aneuploid human tumors. ZW10 and Rod play an essential role in this checkpoint. We show that in mitotic human cells ZW10 resides in a complex with Rod and Zwilch, whereas another ZW10 partner, Zwint-1, is part of a separate complex of structural kinetochore components including Mis12 and Ndc80-Hec1. Zwint-1 is critical for recruiting ZW10 to unattached kinetochores. Depletion from human cells or Xenopus egg extracts is used to demonstrate that the ZW10 complex is essential for stable binding of a Mad1-Mad2 complex to unattached kinetochores. Thus, ZW10 functions as a linker between the core structural elements of the outer kinetochore and components that catalyze generation of the mitotic checkpoint-derived "stop anaphase" inhibitor.

PubMed ID: 15824131
PMC ID: PMC1351127
Article link: J Cell Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bub1 bub1b cdk1 hsp70 hspa1l mad2l1 mis12 mxd1 ndc80 zw10 zwilch
GO keywords: mitotic checkpoint complex

Disease Ontology terms: cancer

Article Images: [+] show captions
References [+] :
Abrieu, Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. 2001, Pubmed, Xenbase