American Association for Cancer Research
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Figure S3 from PKCϵ Controls Mitotic Progression by Regulating Centrosome Migration and Mitotic Spindle Assembly

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posted on 2023-04-03, 17:25 authored by Silvia Martini, Tanya Soliman, Giuliana Gobbi, Prisco Mirandola, Cecilia Carubbi, Elena Masselli, Giulia Pozzi, Peter J. Parker, Marco Vitale

Figure S3. PKCe, p150 (Glued) and Dynein cargo-BubR1 localization upon PKCe or Dynein inhibition.

Funding

Regione Emilia-Romagna Area 1 – Strategic Program 2010-2012

History

ARTICLE ABSTRACT

To form a proper mitotic spindle, centrosomes must be duplicated and driven poleward in a timely and controlled fashion. Improper timing of centrosome separation and errors in mitotic spindle assembly may lead to chromosome instability, a hallmark of cancer. Protein kinase C epsilon (PKCϵ) has recently emerged as a regulator of several cell-cycle processes associated with the resolution of mitotic catenation during the metaphase–anaphase transition and in regulating the abscission checkpoint. However, an engagement of PKCϵ in earlier (pre)mitotic events has not been addressed. Here, we now establish that PKCϵ controls prophase-to-metaphase progression by coordinating centrosome migration and mitotic spindle assembly in transformed cells. This control is exerted through cytoplasmic dynein function. Importantly, it is also demonstrated that the PKCϵ dependency of mitotic spindle organization is correlated with the nonfunctionality of the TOPO2A-dependent G2 checkpoint, a characteristic of many transformed cells. Thus, PKCϵ appears to become specifically engaged in a programme of controls that are required to support cell-cycle progression in transformed cells, advocating for PKCϵ as a potential cancer therapeutic target.Implications: The close relationship between PKCϵ dependency for mitotic spindle organization and the nonfunctionality of the TOPO2A-dependent G2 checkpoint, a hallmark of transformed cells, strongly suggests PKCϵ as a therapeutic target in cancer. Mol Cancer Res; 16(1); 3–15. ©2017 AACR.