EDD, a Ubiquitin-protein Ligase of the N-end Rule Pathway, Associates with Spindle Assembly Checkpoint Components and Regulates the Mitotic Response to Nocodazole

Background: Mitotic progression is regulated by the spindle assembly checkpoint (SAC) to prevent aneuploidy and chromosome damage. Results: EDD binds to various SAC components, governs the expression levels of key mitosis-associated proteins, and mediates the response to the mitotic spindle poison nocodazole. Conclusion: EDD contributes to the ability of the SAC to mediate checkpoint arrest. Significance: EDD may act to maintain genomic integrity. In this work, we identify physical and genetic interactions that implicate E3 identified by differential display (EDD) in promoting spindle assembly checkpoint (SAC) function. During mitosis, the SAC initiates a mitotic checkpoint in response to chromosomes with kinetochores unattached to spindle pole microtubules. Similar to Budding uninhibited by benzimidazoles-related 1 (BUBR1) siRNA, a bona fide SAC component, EDD siRNA abrogated G2/M accumulation in response to the mitotic destabilizing agent nocodazole. Furthermore, EDD siRNA reduced mitotic cell viability and, in nocodazole-treated cells, increased expression of the promitotic progression protein cell division cycle 20 (CDC20). Copurification studies also identified physical interactions with CDC20, BUBR1, and other components of the SAC. Taken together, these observations highlight the potential role of EDD in regulating mitotic progression and the cellular response to perturbed mitosis.

• Publication year

  2015

• Venue

  Journal of Biological Chemistry

• Publication date

  2015-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M114.625673PMID 25833949PMCID 4432279
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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