Open AccessPCTAIRE1 promotes mitotic progression and resistance against antimitotic and apoptotic signals
Author(s) -
Syed Qaaifah Gillani,
Irfana Reshi,
Nusrat Nabi,
Misbah Un Nisa,
Zarka Sarwar,
Sameer Ahmed Bhat,
Thomas M. Roberts,
Jonathan M.G. Higgins,
Shaida Andrabi
Publication year - 2022
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.258831
Subject(s) - mitosis , biology , cytokinesis , midbody , microbiology and biotechnology , polo like kinase , centrosome , mitotic exit , plk1 , cell cycle , spindle checkpoint , cell division , spindle apparatus , cancer research , apoptosis , cell , genetics
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.