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Journal ArticleDOI

Cyclin-dependent kinases: engines, clocks, and microprocessors.

TLDR
This work has shown that Cdk activity is governed by a complex network of regulatory subunits and phosphorylation events whose precise effects on Cdk conformation have been revealed by recent crystallographic studies.
Abstract
Cyclin-dependent kinases (Cdks) play a well-established role in the regulation of the eukaryotic cell division cycle and have also been implicated in the control of gene transcription and other processes. Cdk activity is governed by a complex network of regulatory subunits and phosphorylation events whose precise effects on Cdk conformation have been revealed by recent crystallographic studies. In the cell, these regulatory mechanisms generate an interlinked series of Cdk oscillators that trigger the events of cell division.

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Journal ArticleDOI

From molecular to modular cell biology.

TL;DR: General principles that govern the structure and behaviour of modules may be discovered with help from synthetic sciences such as engineering and computer science, from stronger interactions between experiment and theory in cell biology, and from an appreciation of evolutionary constraints.
Journal ArticleDOI

Differential analysis of gene regulation at transcript resolution with RNA-seq

TL;DR: Cuffdiff 2, an algorithm that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries, robustly identifies differentially expressed transcripts and genes and reveals differential splicing and promoter-preference changes.
Journal ArticleDOI

A quantitative atlas of mitotic phosphorylation.

TL;DR: Analysis of non-proline site-containing phosphopeptides identified two unique motifs that suggest there are at least two undiscovered mitotic kinases, suggesting that many of the proteins identified may be CDK substrates.
Journal ArticleDOI

To cycle or not to cycle: a critical decision in cancer.

TL;DR: Tumour cells undergo uncontrolled proliferation, yet tumours most often originate from adult tissues, in which most cells are quiescent, so the proliferative advantage of tumour cells arises from their ability to bypass quiescence.
References
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Journal ArticleDOI

Cancer Cell Cycles

TL;DR: Genetic alterations affecting p16INK4a and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development.
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A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4

TL;DR: P16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retinoblastoma protein, and inhibits the catalytic activity of theCDK4/cyclin D enzymes.
Journal ArticleDOI

Cell Cycle Checkpoints: Preventing an Identity Crisis

TL;DR: Signal transduction pathways that transmit checkpoint signals in response to DNA damage, replication blocks, and spindle damage are revealed, underscoring the conservation of cell cycle regulatory machinery.
Journal ArticleDOI

Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27

TL;DR: Compared with proliferating cells, quiescent cells exhibited a smaller amount of p27 ubiquitinating activity, which accounted for the marked increase of p 27 half-life measured in these cells, indicating that the abundance of p26 in cells is regulated by degradation.
Journal ArticleDOI

pl5 INK4B is a potentia| effector of TGF-β-induced cell cycle arrest

TL;DR: A new member of the p16INK4 family is isolated, p15INK4B, which is induced ∼30-fold in human keratinocytes by treatment with TGF-β, suggesting that pi5 may act as an effector of T GF-β-mediated cell cycle arrest.
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