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- Publisher Website: 10.1073/pnas.1818820116
- Scopus: eid_2-s2.0-85066803284
- PMID: 31097597
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Article: Role for polo-like kinase 4 in mediation of cytokinesis
Title | Role for polo-like kinase 4 in mediation of cytokinesis |
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Authors | |
Keywords | Polo-like kinase 4 Midbody Cell cycle regulation Centrosome Cytokinesis |
Issue Date | 2019 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2019, v. 116, n. 23, p. 11309-11318 How to Cite? |
Abstract | The mitotic protein polo-like kinase 4 (PLK4) plays a critical role in centrosome duplication for cell division. By using immunofluorescence, we confirm that PLK4 is localized to centrosomes. In addition, we find that phospho-PLK4 (pPLK4) is cleaved and distributed to kinetochores (metaphase and anaphase), spindle midzone/ cleavage furrow (anaphase and telophase), and midbody (cytokinesis) during cell division in immortalized epithelial cells as well as breast, ovarian, and colorectal cancer cells. The distribution of pPLK4 midzone/cleavage furrow and midbody positions pPLK4 to play a functional role in cytokinesis. Indeed, we found that inhibition of PLK4 kinase activity with a small-molecule inhibitor, CFI- 400945, prevents translocation to the spindle midzone/cleavage furrow and prevents cellular abscission, leading to the generation of cells with polyploidy, increased numbers of duplicated centrosomes, and vulnerability to anaphase or mitotic catastrophe. The regulatory role of PLK4 in cytokinesis makes it a potential target for therapeutic intervention in appropriately selected cancers. |
Persistent Identifier | http://hdl.handle.net/10722/292114 |
ISSN | 2021 Impact Factor: 12.779 2020 SCImago Journal Rankings: 5.011 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Press, Michael F. | - |
dc.contributor.author | Xie, Bin | - |
dc.contributor.author | Davenport, Simon | - |
dc.contributor.author | Zhou, Yu | - |
dc.contributor.author | Guzman, Roberta | - |
dc.contributor.author | Nolan, Garry P. | - |
dc.contributor.author | O'Brien, Neil | - |
dc.contributor.author | Palazzolo, Michael | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Brugge, Joan S. | - |
dc.contributor.author | Slamon, Dennis J. | - |
dc.date.accessioned | 2020-11-17T14:55:47Z | - |
dc.date.available | 2020-11-17T14:55:47Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2019, v. 116, n. 23, p. 11309-11318 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292114 | - |
dc.description.abstract | The mitotic protein polo-like kinase 4 (PLK4) plays a critical role in centrosome duplication for cell division. By using immunofluorescence, we confirm that PLK4 is localized to centrosomes. In addition, we find that phospho-PLK4 (pPLK4) is cleaved and distributed to kinetochores (metaphase and anaphase), spindle midzone/ cleavage furrow (anaphase and telophase), and midbody (cytokinesis) during cell division in immortalized epithelial cells as well as breast, ovarian, and colorectal cancer cells. The distribution of pPLK4 midzone/cleavage furrow and midbody positions pPLK4 to play a functional role in cytokinesis. Indeed, we found that inhibition of PLK4 kinase activity with a small-molecule inhibitor, CFI- 400945, prevents translocation to the spindle midzone/cleavage furrow and prevents cellular abscission, leading to the generation of cells with polyploidy, increased numbers of duplicated centrosomes, and vulnerability to anaphase or mitotic catastrophe. The regulatory role of PLK4 in cytokinesis makes it a potential target for therapeutic intervention in appropriately selected cancers. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Polo-like kinase 4 | - |
dc.subject | Midbody | - |
dc.subject | Cell cycle regulation | - |
dc.subject | Centrosome | - |
dc.subject | Cytokinesis | - |
dc.title | Role for polo-like kinase 4 in mediation of cytokinesis | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1073/pnas.1818820116 | - |
dc.identifier.pmid | 31097597 | - |
dc.identifier.pmcid | PMC6561306 | - |
dc.identifier.scopus | eid_2-s2.0-85066803284 | - |
dc.identifier.volume | 116 | - |
dc.identifier.issue | 23 | - |
dc.identifier.spage | 11309 | - |
dc.identifier.epage | 11318 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:000470136000040 | - |
dc.identifier.issnl | 0027-8424 | - |