Abstract
BackgroundCDK11p58 is a mitotic protein kinase, which has been shown to be required for different mitotic events such as centrosome maturation, chromatid cohesion and cytokinesis.Methodology/Principal FindingsIn addition to these previously described roles, our study shows that CDK11p58 inhibition induces a failure in the centriole duplication process in different human cell lines. We propose that this effect is mediated by the defective centrosomal recruitment of proteins at the onset of mitosis. Indeed, Plk4 protein kinase and the centrosomal protein Cep192, which are key components of the centriole duplication machinery, showed reduced levels at centrosomes of mitotic CDK11-depleted cells. CDK11p58, which accumulates only in the vicinity of mitotic centrosomes, directly interacts with the centriole-associated protein kinase Plk4 that regulates centriole number in cells. In addition, we show that centriole from CDK11 defective cells are not able to be over duplicated following Plk4 overexpression.Conclusion/SignificanceWe thus propose that CDK11 is required for centriole duplication by two non-mutually-exclusive mechanisms. On one hand, the observed duplication defect could be caused indirectly by a failure of the centrosome to fully maturate during mitosis. On the other hand, CDK11p58 could also directly regulate key centriole components such as Plk4 during mitosis to trigger essential mitotic centriole modifications, required for centriole duplication during subsequent interphase.
Highlights
The centrosome of somatic cells is the main microtubule organising center [1]
We have shown previously that CDK11p58 is required for centrosome maturation (Petretti et al, 2006)
Our study reveals that the mitotic specific CDK11p58 is able to associate with Plk4 during mitosis and is required to target the Plk4 protein kinase to the centrosome in mitosis
Summary
The centrosome of somatic cells is the main microtubule organising center [1]. It is required to organise the cytoplasmic microtubule network during interphase and the mitotic spindle during mitosis. In proliferating cells before division, the centrosome needs to be duplicated precisely once so that the mitotic cell harbours two centrosomes, each comprising two centrioles These two centrosomes will be used to nucleate the microtubules required to assemble the mitotic bipolar spindle during mitosis [2]. In late G2, as cells prepare for mitosis, centrosomes increase in size and recruit additional PCM to enhance their ability to nucleate microtubules. This process is referred to as centrosome maturation. At the end of the G2 phase, the two newly duplicated centrosomes separate to organise a bipolar mitotic spindle, enabling each daughter cell to inherit one centrosome after cell division. CDK11p58 is a mitotic protein kinase, which has been shown to be required for different mitotic events such as centrosome maturation, chromatid cohesion and cytokinesis
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