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Inhibition of polo-like kinase 1 suppresses microtubule dynamics in MCF-7 cells

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Abstract

Polo-like kinase 1 (Plk1) is a mitotic serine/threonine kinase implicated in spindle formation and cytokinesis in mammalian cells. Here, purified Plk1 was found to bind to reconstituted microtubules in vitro. Further, Plk1 was found to co-localize with interphase microtubules in MCF-7 cells and to co-immunoprecipitate with polymerized tubulin. The binding of Plk1 to interphase microtubules appeared to increase with an increase in the level of tubulin acetylation in MCF-7 cells. Interestingly, Plk1 inhibitor III, an inhibitor of Plk1 kinase activity, treatment increased the association of Plk1 with the interphase microtubules in MCF-7 cells. Therefore, the effect of inhibition of Plk1 kinase activity on the dynamic instability of microtubules was determined by time-lapse imaging in MCF-7 cells. Plk1 inhibitor III dampened the dynamic instability of microtubules. For example, Plk1 inhibitor III (3 μM) reduced the rate and extent of the growing phase by 28 and 48%, respectively, and inhibited the dynamicity of microtubules by 53% as compared to the microtubules in control MCF-7 cells. Plk1 inhibitor III treatment also increased the level of acetylated microtubules, indicating that it stabilizes microtubules. The findings indicated that Plk1 interacts with microtubules and Plk1 may have a role in the regulation of microtubule dynamics.

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Abbreviations

TSA:

Trichostatin A

Plk1:

Polo-like kinase 1

HDAC6:

Histone deacetylase 6

IC50 :

Half-maximal proliferation inhibitory concentration

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Acknowledgements

The work is supported by a Grant from the Department of Biotechnology, Government of India (BT/PR13319/BRB/10/762/2009), to DP. We gratefully acknowledge the confocal laser scanning microscope of the Central Facility, IIT Bombay.

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Authors and Affiliations

  1. Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India

    Aijaz Rashid, Afsana Naaz, Ankit Rai, Biswa Prasun Chatterji & Dulal Panda

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  1. Aijaz Rashid
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  2. Afsana Naaz
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Correspondence to Dulal Panda.

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Rashid, A., Naaz, A., Rai, A. et al. Inhibition of polo-like kinase 1 suppresses microtubule dynamics in MCF-7 cells. Mol Cell Biochem 465, 27–36 (2020). https://doi.org/10.1007/s11010-019-03664-y

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