The Ki-67 and Repoman mitotic phosphatases assemble via an identical, yet novel mechanism
| Autor: | Sofie De Munter, Mathieu Bollen, Ezgi Gokhan, Ganesan Senthil Kumar, Rebecca Page, Paola Vagnarelli, Wolfgang Peti |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Magnetic Resonance Spectroscopy Protein Conformation Cell Cycle Proteins Crystallography X-Ray 0302 clinical medicine Holoenzymes Protein Phosphatase 1 structural biology protein phosphatase 1 (PP1) Biology (General) Cancer Biology Anaphase General Neuroscience Nuclear Proteins General Medicine Cell cycle Biophysics and Structural Biology Chicken 3. Good health Cell biology Chromatin embryonic structures RepoMan Ki-67 Medicine cell cycle biological phenomena cell phenomena and immunity Human animal structures QH301-705.5 Science Aurora B kinase macromolecular substances Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Humans cancer Mitosis General Immunology and Microbiology E. coli Protein phosphatase 1 enzymes and coenzymes (carbohydrates) Ki-67 Antigen 030104 developmental biology Mitotic exit Protein Multimerization Research Advance Carrier Proteins 030217 neurology & neurosurgery |
| Zdroj: | eLife, Vol 5 (2016) eLife |
| Popis: | Ki-67 and RepoMan have key roles during mitotic exit. Previously, we showed that Ki-67 organizes the mitotic chromosome periphery and recruits protein phosphatase 1 (PP1) to chromatin at anaphase onset, in a similar manner as RepoMan (Booth et al., 2014). Here we show how Ki-67 and RepoMan form mitotic exit phosphatases by recruiting PP1, how they distinguish between distinct PP1 isoforms and how the assembly of these two holoenzymes are dynamically regulated by Aurora B kinase during mitosis. Unexpectedly, our data also reveal that Ki-67 and RepoMan bind PP1 using an identical, yet novel mechanism, interacting with a PP1 pocket that is engaged only by these two PP1 regulators. These findings not only show how two distinct mitotic exit phosphatases are recruited to their substrates, but also provide immediate opportunities for the design of novel cancer therapeutics that selectively target the Ki-67:PP1 and RepoMan:PP1 holoenzymes. ispartof: Elife vol:5 issue:AUGUST ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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