2. Academic Validation
  3. BuGZ is required for Bub3 stability, Bub1 kinetochore function, and chromosome alignment

BuGZ is required for Bub3 stability, Bub1 kinetochore function, and chromosome alignment

  • Dev Cell. 2014 Feb 10;28(3):282-94. doi: 10.1016/j.devcel.2013.12.014.
Chad M Toledo 1,  Jacob A Herman 2,  Jonathan B Olsen 3,  Yu Ding 4,  Philip Corrin 4,  Emily J Girard 5,  James M Olson 5,  Andrew Emili 3,  Jennifer G DeLuca 6,  Patrick J Paddison 7
Affiliations

Affiliations

  • 1 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
  • 2 Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
  • 3 Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
  • 4 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • 5 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • 6 Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA. Electronic address: jennifer.deluca@colostate.edu.
  • 7 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA. Electronic address: paddison@fhcrc.org.
PMID: 24462187 DOI: 10.1016/j.devcel.2013.12.014
Abstract

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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