EDD, a Ubiquitin-Protein Ligase of the N-end Rule Pathway, Associates with Spindle Assembly Checkpoint Components and Regulates the Mitotic Response to Nocodazole. [Signal Transduction]

April 1st, 2015 by Scialpi, F., Mellis, D., Ditzel, M.

In this work we identify physical and genetic interactions that implicate the 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 a G2/M accumulation in response to the mitotic destabilising agent Nocodazole (Noc). Furthermore, EDD siRNA reduced mitotic cell viability and, in Noc-treated cells, increased expression of the pro-mitotic-progression protein Cell division cycle 20 (CDC20). Co-purification studies also identified physical interactions with CDC20, BUBR1 and other components of the SAC. Taken together these observations highlight EDDs potential role in regulating mitotic progression and the cellular response to perturbed mitoses.
  • Posted in Journal of Biological Chemistry, Publications
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