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- W2950270988 abstract "Proliferation is driven by an intricate machinery, the smooth operation of which is essential for the development and survival of the organism. The central task of this machinery is to copy the genetic material of a dividing cell and to distribute it evenly between daughter cells. Yet, in higher eukaryotes, the division of every single cell has to be coordinated with the development of the whole organism. Mistakes in this cell cycle program are rarely tolerated: they give rise to developmental aberrations or cancer and often lead to the organism's demise.A collaborative effort from many laboratories has transformed our understanding of the cell cycle from a black box to an amazing level of molecular detail. Early groundbreaking studies revealed the crucial role of oscillating kinase activities in driving the embryonic cell cycle1–4. The activation of a kinase, which was first referred to as maturation-promoting factor and later identified to be cyclin-dependent kinase Cdk1, was shown to trigger entry of cells into mitosis. Its capability to phosphorylate its substrates is dependent on the periodic synthesis of essential cyclin subunits5–7. Consequently, the removal of cyclins shuts down Cdk1 and leads to exit from mitosis. It was soon realized that ]cyclins are disposed of by ubiquitin-proteasome dependent degradation8, which brought ubiquitination into the limelight of cell cycle control.Subsequent studies extended the role of ubiquitination in regulating proliferation far beyond its part in the tug-of-war between kinase-activation and protein degradation. Ubiquitination also regulates checkpoints that ensure the high fidelity of cell division, and signaling networks that couple proliferation to differentiation and development. Such a powerful role in cell cycle control comes with its own risk, and many malignancies result from aberrant ubiquitination. In this review, we will discuss key concepts which illustrate how ubiquitination regulates cell cycle progression, and how its misregulation can trigger aberrant proliferation and cancer." @default.
- W2950270988 created "2019-06-27" @default.
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- W2950270988 date "2009-06-30" @default.
- W2950270988 modified "2023-09-26" @default.
- W2950270988 title "ChemInform Abstract: The Multiple Layers of Ubiquitin-Dependent Cell Cycle Control" @default.
- W2950270988 cites W1976091944 @default.
- W2950270988 doi "https://doi.org/10.1002/chin.200926267" @default.
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