期刊
DEVELOPMENTAL CELL
卷 28, 期 3, 页码 282-294出版社
CELL PRESS
DOI: 10.1016/j.devcel.2013.12.014
关键词
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资金
- National Science Foundation Graduate Research Fellowship Program [DGE-0-718124, DGE-1256082]
- Accelerate Brain Cancer Cure
- DoD Translational New Investigator Award [CA100735]
- NIH [R21CA170722-01, P30CA15704, R01 GM088371]
- Pew Biomedical Scholars Program
- Phi Beta Psi Sorority Cancer Research Grant
- CDMRP [CA100735, 545629] Funding Source: Federal RePORTER
During mitosis, the spindle assembly checkpoint (SAC) monitors the attachment of kinetochores (KTs) to the plus ends of spindle microtubules (MTs) and prevents anaphase onset until chromosomes are aligned and KTs are under proper tension. Here, we identify a SAC component, BuGZ/ZNF207, from an RNAi viability screen in human glioblastoma multiforme (GBM) brain tumor stem cells. BuGZ binds to and stabilizes Bub3 during interphase and mitosis through a highly conserved GLE2p-binding sequence (GLEBS) domain. Inhibition of BuGZ results in loss of both Bub3 and its binding partner Bub1 from KTs, reduction of Bub1 -dependent phosphorylation of centromeric histone H2A, attenuation of KT-based Aurora B kinase activity, and lethal chromosome congression defects in cancer cells. Phylogenetic analysis indicates that BuGZ orthologs are highly, conserved among eukaryotes, but are conspicuously absent from budding and fission yeasts. These findings suggest that BuGZ has evolved to facilitate Bub3 activity and chromosome congression in higher eukaryotes.
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