期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 23, 页码 11309-11318出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1818820116
关键词
polo-like kinase 4; cell cycle regulation; cytokinesis; centrosome; midbody
资金
- National Cancer Institute Cancer Center Shared Grant [P30CA014089]
- USC Office of the Provost, Dean's Development Funds, Keck School ofMedicine of USC
- California Institute for Regenerative Medicine [DR1-01477, 1559-S-NA228, DR3-07067, 1559-S-SA669]
- Dr. Miriam & Sheldon G. Adelson Medical Research Foundation
- Breast Cancer Research Foundation [BCRF-18-132]
- Tower Cancer Research Foundation Jessica M. Berman Senior Investigator Award [0068860001]
- Avon Foundation for Women [02-2015-062]
- endowed Harold E. Lee Chair for Cancer Research
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据