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. 2011 Jan 27;6:2.
doi: 10.1186/1747-1028-6-2.

The G1 Phase Cdks Regulate the Centrosome Cycle and Mediate Oncogene-Dependent Centrosome Amplification

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Free PMC article

The G1 Phase Cdks Regulate the Centrosome Cycle and Mediate Oncogene-Dependent Centrosome Amplification

Mary K Harrison et al. Cell Div. .
Free PMC article

Abstract

Because centrosome amplification generates aneuploidy and since centrosome amplification is ubiquitous in human tumors, a strong case is made for centrosome amplification being a major force in tumor biogenesis. Various evidence showing that oncogenes and altered tumor suppressors lead to centrosome amplification and aneuploidy suggests that oncogenes and altered tumor suppressors are a major source of genomic instability in tumors, and that they generate those abnormal processes to initiate and sustain tumorigenesis. We discuss how altered tumor suppressors and oncogenes utilize the cell cycle regulatory machinery to signal centrosome amplification and aneuploidy.

Figures

Figure 1
Figure 1
The G1 phase Cdks and the E2Fs regulate various steps in the centrosome duplication cycle. Various evidence suggests that the G1 phase Cdks directly phosphorylate NPM, CP110 and Mps1 to regulate centrosome licensing and duplication. The dotted line reflects the fact that even though Plk4 is not a direct target of Cdk2, introduction of a dominant-negative Cdk2 construct renders it ineffective in triggering centriole reduplication. The figure reflects how the E2F activators E2F1, E2F2 and E2F3 influence the centrosome duplication cycle by controlling the transcriptional levels of cyclins E, A, D, and Cdk2. The figure also reflects how E2F3 and E2F4 repress cyclin E and Nek2 to influence the centrosome cycle.

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