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The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells
Journal article   Open access   Peer reviewed

The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells

Cristina M Cummings, Cornelia A Bentley, Sarah A Perdue, Peter W Baas and Jeffrey D Singer
The Journal of biological chemistry, v 284(17), pp 11663-11675
24 Apr 2009
DOI: https://doi.org/10.1074/jbc.M809374200
PMID: 19261606
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1074/jbc.M809374200View
Published, Version of Record (VoR) Open

Abstract

Protein Structure, Tertiary Amino Acid Sequence Mitosis Humans Gene Expression Regulation Ubiquitin-Protein Ligases - metabolism Molecular Sequence Data Cullin Proteins - physiology Ubiquitin-Protein Ligases - chemistry Ubiquitin-Protein Ligases - physiology Cullin Proteins - chemistry Two-Hybrid System Techniques Microtubules - metabolism Models, Biological Adenosine Triphosphatases - chemistry Katanin HeLa Cells Adenosine Triphosphatases - physiology
The proper regulation of factors involved in mitosis is crucial to ensure normal cell division. Levels and activities of proteins are regulated in many ways, one of which is ubiquitin-mediated protein degradation. E3 ubiquitin ligases are involved in targeting specific substrates for degradation by facilitating their ubiquitination. In seeking to elucidate additional biological roles for Cul3 we performed a two-hybrid screen and identified Ctb9/KLHDC5 as a Cul3-interacting protein. Overexpression of Ctb9/KLHDC5 resulted in an increase in microtubule density as well as persistent microtubule bridges between post-mitotic cells. Conversely, down-regulation of Ctb9/KLHDC5 showed a pronounced reduction in microtubule density. Based on these observations, we examined the interactions between Cul3, Ctb9/KLHDC5, and the microtubule-severing protein, p60/katanin. Here we show that p60/katanin interacts with a complex consisting of Cul3 and Ctb9/KLHDC5, which results in ubiquitin laddering of p60/katanin. Also, Cul3-deficient cells or Ctb9/KLHDC5-deficient cells show an increase in p60/katanin levels, indicating that Cul3/Ctb9/KLHDC5 is required for efficient p60/katanin removal. We demonstrate a novel regulatory mechanism for p60/katanin that occurs at the level of targeted proteolysis to allow normal mitotic progression in mammalian cells.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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