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 non-functionality 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.

PKCε Controls Mitotic Progression by Regulating Centrosome Migration and Mitotic Spindle Assembly / Martini, Silvia; Soliman, Tanya; Gobbi, Giuliana; Mirandola, Prisco; Carubbi, Cecilia; Masselli, Elena; Pozzi, Giulia; Parker, Peter J; Vitale, Marco. - In: MOLECULAR CANCER RESEARCH. - ISSN 1541-7786. - (2018), p. molcanres.0244.2017. [10.1158/1541-7786.MCR-17-0244]

PKCε Controls Mitotic Progression by Regulating Centrosome Migration and Mitotic Spindle Assembly

VITALE, Marco
2018-01-01

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 non-functionality 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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/154061
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 17
social impact