Cyclin A/Cdk2 regulates Cdh1 and claspin during late S/G2 phase of the cell cycle.

Whereas many components regulating the progression from S phase through G2 phase into mitosis have been identified, the mechanism by which these components control this critical cell cycle progression is still not fully elucidated. Cyclin A/Cdk2 has been shown to regulate the timing of Cyclin B/Cdk1 activation and progression into mitosis although the mechanism by which this occurs is only poorly understood. Here we show that depletion of Cyclin A or inhibition of Cdk2 during late S/early G2 phase maintains the G2 phase arrest by reducing Cdh1 transcript and protein levels, thereby stabilizing Claspin and maintaining elevated levels of activated Chk1 which contributes to the G2 phase observed.

A potent Chk1 inhibitor is selectively cytotoxic in melanomas with high levels of replicative stress.

There are few effective treatments for metastatic melanoma. Checkpoint kinase 1 (Chk1) inhibitors are being trialled for their efficacy in enhancing conventional chemotherapeutic agents, but their effectiveness as single agents is not known. We have examined the effectiveness of two novel Chk1 selective inhibitors, AR323 and AR678, in a panel of melanoma cell lines and normal cell types.

The histone deacetylase inhibitor MGCD0103 has both deacetylase and microtubule inhibitory activity.

Histone deacetylase inhibitors (HDACis) are currently in trial or are in clinical use for the treatment of a number of tumor types. The clinical efficacy of HDACis can be partly attributed to the modulation of the cell cycle by the HDACis. Here, we have examined the effects of N-(2-aminophenyl)-4-((4-pyridin-3-ylpyrimidin-2-ylamino)methyl)benzamide (MGCD0103), a class I-selective histone deacetylase inhibitor, on the cell cycle and cell killing.

Cyclin A/cdk2 regulates adenomatous polyposis coli-dependent mitotic spindle anchoring.

Mutations in adenomatous polyposis coli (APC) protein is a major contributor to tumor initiation and progression in several tumor types. These mutations affect APC function in the Wnt-beta-catenin signaling and influence mitotic spindle anchoring to the cell cortex and orientation. Here we report that the mitotic anchoring and orientation function of APC is regulated by cyclin A/cdk2.

Convergent antifouling activities of structurally distinct bioactive compounds synthesized within two sympatric Haliclona demosponges.

A wide range of sessile and sedentary marine invertebrates synthesize secondary metabolites that have potential as industrial antifoulants. These antifoulants tend to differ in structure, even between closely related species. Here, we determine if structurally divergent secondary metabolites produced within two sympatric haliclonid demosponges have similar effects on the larvae of a wide range of benthic competitors and potential fouling metazoans (ascidians, molluscs, bryozoans, polychaetes, and sponges).