Post-translational control of transcription factors: methylation ranks highly.

Methylation of lysine and arginine residues on histones has long been known to determine both chromatin structure and gene expression. In recent years, the methylation of non-histone proteins has emerged as a prevalent modification which impacts on diverse processes such as cell cycle control, DNA repair, senescence, differentiation, apoptosis and tumourigenesis. Many of these non-histone targets represent transcription factors, cell signalling molecules and tumour suppressor proteins. Evidence now suggests that the dysregulation of methyltransferases, demethylases and reader proteins is involved in the development of many diseases, including cancer, and several of these proteins represent potential therapeutic targets for small molecule compounds, fuelling a recent surge in chemical inhibitor design. Such molecules will greatly help us to understand the role of methylation in both health and disease.

To live or let die - complexity within the E2F1 pathway.

The E2F1 transcription factor is a recognized regulator of the cell cycle as well as a potent mediator of DNA damage-induced apoptosis and the checkpoint response. Understanding the diverse and seemingly dichotomous functions of E2F1 activity has been the focus of extensive ongoing research. Although the E2F pathway is frequently deregulated in cancer, the contributions of E2F1 itself to tumorigenesis, as a promoter of proliferation or cell death, are far from understood. In this review we aim to provide an update on our current understanding of E2F1, with particular insight into its novel interaction partners and post-translational modifications, as a means to explaining its diverse functional complexity.

Permanent pacemakers for paroxysmal tachycardia.

In this paper the various types of permanent antetachycardia pacemakers are discussed, whether they be patient activated or fully automatic. Simple underdrive and burst overdrive pacemakers are discussed and the more advanced burst pacing systems that are under evaluation at present are also described. The most recent advances in this field have occurred in relation to the development of adaptive extra stimulus pacemakers and these are discussed in greater detail. Finally the author's view on future developments in this field are outlined.