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Volume 3 Issue 3, March 2007

A clickable inhibitor reveals context-dependent autoactivation of p90 RSK. Cohen et al. (p 156) generated fmk-pa, a potent inhibitor of the p90 ribosomal S6 kinases RSK1 and RSK2. The authors used click chemistry to show specific and irreversible modification of RSKs in mammalian cells. RSKs are activated by the MEK-ERK signal transduction pathway through phosphorylation of the C-terminal kinase domain (CTD), which goes on to phosphorylate and activate the N-terminal kinase domain (NTD). Using their inhibitor, the authors found evidence for an unidentified kinase that bypasses RSK CTD activity. The cover illustrates CTD inhibition by fmk-pa, which should have cellular effects that are distinct from those of NTD inhibition by the recently reported compound BI-D1870 (see also News & Views by Frödin, p 138). Cover art by Erin Boyle, based on images and design provided by Michael Cohen.

Editorial

  • Scientists from across the chemistry and biology communities often have divergent ideas of what constitutes mechanistic insight into a biological system. Science that forges a middle ground between these disciplines offers the best way forward for chemical biologists.

    Editorial

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Commentary

  • The broad range of techniques used in chemical biology presents many challenges in reporting, translating and implementing experimental knowledge. By taking advantage of some readily available solutions and instituting some new approaches, it should be possible to more effectively disseminate technological advances.

    • Stefan Lutz
    Commentary
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Meeting Report

  • Chemical and genetic approaches are extensively used to probe living systems at the subcellular level and to advance therapeutic target discovery. The 2006 American Society for Cell Biology meeting highlighted the growing importance of chemical biology approaches in cell biology research.

    • Rami N Hannoush
    Meeting Report
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News & Views

  • The zebrafish is a highly promising model system for vertebrate genetics study, but the temporal control of gene expression has remained underdeveloped. A new chemical genetic system using a small-molecule switch for protein synthesis promises to increase the usefulness of the zebrafish as a vertebrate model system.

    • Young-Tae Chang
    News & Views
  • Short double-stranded RNA duplexes are the triggers for post-transcriptional gene silencing and can also induce epigenetic silencing of genes at the level of transcription. A surprising new finding is that short RNA duplexes targeted to promoter regions can also mediate potent enhancement of transcription.

    • John J Rossi
    News & Views
  • The presence of 491 very similar protein kinases in humans has proven to be a serious obstacle to generating specific kinase inhibitors and assessing their selectivity. Now, rational drug design has led to the generation of an irreversible kinase inhibitor with built-in features for demonstrating specificity in cells.

    • Morten Frödin
    News & Views
  • The circadian clock runs with a period of about 24 h and therefore allows mammals to predict sunrise at the cellular level. Phosphorylation of the clock protein period 2 influences this process by varying the clock's period length.

    • Urs Albrecht
    News & Views
  • Despite having an increasingly accurate parts list for biological cells, much is left to discover about how these parts act together to create functional cells, and how distinct individual cells interact to create functional tissues and organs. Biologists are increasingly aware of the cell-to-cell variability in molecule copy numbers—a trend that is revealed by several new techniques, including one that permits counting molecules in single cells.

    • G Balázsi
    • J J Collins
    News & Views
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Review Article

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Brief Communication

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Letter

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Article

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Corrigendum

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