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PLoS One. 2018 Jan 2;13(1):e0190513. doi: 10.1371/journal.pone.0190513. eCollection 2018.

USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation.

Author information

1
Imperial College London, Department of Medicine, Division of Infectious Diseases, Norfolk Place, London, United Kingdom.
2
Francis Crick Institute, The Crick Mass Spectrometry Science Technology Platform, 1 Midland Road, London, United Kingdom.

Abstract

Correct segregation of the mitotic chromosomes into daughter cells is a highly regulated process critical to safeguard genome stability. During M phase the spindle assembly checkpoint (SAC) ensures that all kinetochores are correctly attached before its inactivation allows progression into anaphase. Upon SAC inactivation, the anaphase promoting complex/cyclosome (APC/C) E3 ligase ubiquitinates and targets cyclin B and securin for proteasomal degradation. Here, we describe the identification of Ribonucleic Acid Export protein 1 (RAE1), a protein previously shown to be involved in SAC regulation and bipolar spindle formation, as a novel substrate of the deubiquitinating enzyme (DUB) Ubiquitin Specific Protease 11 (USP11). Lentiviral knock-down of USP11 or RAE1 in U2OS cells drastically reduces cell proliferation and increases multipolar spindle formation. We show that USP11 is associated with the mitotic spindle, does not regulate SAC inactivation, but controls ubiquitination of RAE1 at the mitotic spindle, hereby functionally modulating its interaction with Nuclear Mitotic Apparatus protein (NuMA).

PMID:
29293652
PMCID:
PMC5749825
DOI:
10.1371/journal.pone.0190513
[Indexed for MEDLINE]
Free PMC Article

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