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

Autor: Ambrosius P. Snijders, Anna Stockum, Goedele N. Maertens
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Nucleocytoplasmic Transport Proteins
Molecular biology
Cyclin B
lcsh:Medicine
Biochemistry
Substrate Specificity
Ligases
Nuclear Matrix-Associated Proteins
Cell Cycle and Cell Division
Post-Translational Modification
lcsh:Science
Anaphase
Staining
Multidisciplinary
biology
Chemistry
Kinetochore
Intracellular Signaling Peptides and Proteins
Cell Staining
Cell biology
Enzymes
Spindle checkpoint
Securin
Cell Processes
Gene Knockdown Techniques
293T cells
Cell lines
Biological cultures
Protein Binding
Research Article
General Science & Technology
Spindle Apparatus
DNA construction
03 medical and health sciences
Cell Line
Tumor
Cyclins
MD Multidisciplinary
Humans
Metaphase
Cell Proliferation
lcsh:R
Ubiquitination
Biology and Life Sciences
Proteins
Cell Biology
Spindle apparatus
Research and analysis methods
030104 developmental biology
HEK293 Cells
Molecular biology techniques
Specimen Preparation and Treatment
Plasmid Construction
biology.protein
Enzymology
lcsh:Q
Thiolester Hydrolases
Anaphase-promoting complex
Multipolar spindles
Zdroj: PLoS ONE, Vol 13, Iss 1, p e0190513 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: 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).
Databáze: OpenAIRE
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