The HECT E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint

Evan C. Osmundson, Dipankar Ray, Finola E. Moore, Qingshen Gao, Gerald H. Thomsen, Hiroaki Kiyokawa*

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Activation of the anaphase-promoting complex/cyclosome (APC/C) by Cdc20 is critical for the metaphase-anaphase transition. APC/C-Cdc20 is required for polyubiquitination and degradation of securin and cyclin B at anaphase onset. The spindle assembly checkpoint delays APC/C-Cdc20 activation until all kinetochores attach to mitotic spindles. In this study, we demonstrate that a HECT (homologous to the E6-AP carboxyl terminus) ubiquitin ligase, Smurf2, is required for the spindle checkpoint. Smurf2 localizes to the centrosome, mitotic midbody, and centromeres. Smurf2 depletion or the expression of a catalytically inactive Smurf2 results in misaligned and lagging chromosomes, premature anaphase onset, and defective cytokinesis. Smurf2 inactivation prevents nocodazole-treated cells from accumulating cyclin B and securin and prometa-phase arrest. The silencing of Cdc20 in Smurf2-depleted cells restores mitotic accumulation of cyclin B and securin. Smurf2 depletion results in enhanced polyubiquitination and degradation of Mad2, a critical checkpoint effector. Mad2 is mislocalized in Smurf2-depleted cells, suggesting that Smurf2 regulates the localization and stability of Mad2. These data indicate that Smurf2 is a novel mitotic regulator.

Original languageEnglish (US)
Pages (from-to)267-277
Number of pages11
JournalJournal of Cell Biology
Volume183
Issue number2
DOIs
StatePublished - Oct 20 2008

ASJC Scopus subject areas

  • Cell Biology

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