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PCTAIRE1 promotes mitotic progression and resistance against antimitotic and apoptotic signals
Syed Qaaifah Gillani1, Irfana Reshi2, Nusrat Nabi1
1Department of Biochemistry, University of Kashmir, Srinagar 190006, India.
Abstract:
PCTAIRE1 (also known as CDK16) is a serine-threonine kinase implicated in physiological processes like neuronal development, vesicle trafficking, spermatogenesis and cell proliferation. However, its exact role in cell division remains unclear. In this study, using a library screening approach, we identified PCTAIRE1 among several candidates that resisted mitotic arrest and mitotic cell death induced by polyomavirus small T (PolST) expression in mammalian cells. Our study showed that PCTAIRE1 is a mitotic kinase that localizes at centrosomes during G2 and at spindle poles as the cells enter mitosis, and then at the midbody during cytokinesis. We also report that PCTAIRE1 protein levels fluctuate through the cell cycle and reach their peak at mitosis, during which there is an increase in PCTAIRE1 phosphorylation as well. Interestingly, knockdown of PCTAIRE1 resulted in aberrant mitosis by interfering with spindle assembly and chromosome segregation. Further, we found that PCTAIRE1 promotes resistance of cancer cells to antimitotic drugs, and this underscores the significance of PCTAIRE1 as a potential drug target for overcoming chemotherapeutic resistance. Taken together, these studies establish PCTAIRE1 as a critical mediator of mitotic progression and highlight its role in chemotherapeutic resistance. This article has an associated First Person interview with the first author of the paper.
Insights
PCTAIRE1 (CDK16) is a crucial mitotic kinase regulating cell division and centrosome function. Its role in resisting cancer cell death from antimitotic drugs highlights its potential as a therapeutic target.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- PCTAIRE1 (CDK16) is a serine-threonine kinase involved in various physiological processes.
- Its precise function during cell division has not been fully elucidated.
- Understanding PCTAIRE1's role is crucial for comprehending cell cycle regulation.
Purpose of the Study:
- To investigate the role of PCTAIRE1 in cell division and mitotic progression.
- To determine PCTAIRE1's localization and regulation during the cell cycle.
- To explore PCTAIRE1's involvement in cancer cell resistance to antimitotic drugs.
Main Methods:
- Library screening to identify proteins involved in mitotic arrest resistance.
- Immunofluorescence microscopy to track PCTAIRE1 localization.
- Cell cycle analysis and Western blotting to assess protein levels and phosphorylation.
- PCTAIRE1 knockdown experiments to evaluate its functional impact on mitosis.
- Assessment of cancer cell response to antimitotic drugs following PCTAIRE1 manipulation.
Main Results:
- PCTAIRE1 was identified as a kinase that confers resistance to mitotic arrest.
- PCTAIRE1 localizes to centrosomes, spindle poles, and the midbody during mitosis and cytokinesis.
- PCTAIRE1 protein levels and phosphorylation peak during mitosis.
- Knockdown of PCTAIRE1 leads to aberrant spindle assembly and chromosome segregation.
- PCTAIRE1 enhances cancer cell resistance to antimitotic chemotherapeutic agents.
Conclusions:
- PCTAIRE1 is a critical mediator of mitotic progression and cytokinesis.
- PCTAIRE1 plays a significant role in conferring resistance to antimitotic drugs in cancer cells.
- PCTAIRE1 represents a potential therapeutic target for overcoming chemotherapy resistance.
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