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PCTAIRE1 promotes mitotic progression and resistance against antimitotic and apoptotic signals

Lookup NU author(s): Syed Gillani, Professor Jonathan HigginsORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2022. Published by The Company of Biologists Ltd. 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.


Publication metadata

Author(s): Gillani SQ, Reshi I, Nabi N, Nisa MU, Sarwar Z, Bhat S, Roberts TM, Higgins JMG, Andrabi S

Publication type: Article

Publication status: Published

Journal: Journal of Cell Science

Year: 2022

Volume: 135

Issue: 3

Online publication date: 09/02/2022

Acceptance date: 29/12/2021

Date deposited: 10/03/2022

ISSN (print): 0021-9533

ISSN (electronic): 1477-9137

Publisher: Company of Biologists Ltd

URL: https://doi.org/10.1242/jcs.258831

DOI: 10.1242/jcs.258831

PubMed id: 35044463


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Funding

Funder referenceFunder name
BT/PR13605/MED/30/1525/2015

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