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Volume 28 Issue 7, July 2010

Crystal structure of the WD40 domain of the yeast SCFCdc4 E3 ubiquitin ligase showing the binding of an allosteric inhibitor and the subsequent displacement of the substrate. Orlicky et al. and Aghajan et al. present the first inhibitors of cullin-RING ubiquitin ligases, the largest class of enzyme that confers specificity to the ubiquitin-proteasome system. (pp 733 and 738).

Volume 28 Issue 7

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Editorial

  • The rise of open source drug R&D in consortia involving big pharma should prompt some biotech companies to re-examine their businesses.

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News

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Data Page

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News Feature

  • US drug companies are preparing for new draconian provisions for reporting on financial relationships with academia. Will efforts to increase transparency prove burdensome to researchers and the industry? Virginia Hughes investigates.

    • Virginia Hughes
    News Feature
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Correspondence

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Commentary

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Feature

  • Improvements in technology are making proteomics research less descriptive and more analytic, but the field has yet to deliver on its aspirations.

    • Peter Mitchell
    Feature
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Patents

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News & Views

  • A new method for characterizing signaling responses to pairs of agonists predicts how cells react to higher-order combinations of external stimuli.

    • Kevin A Janes
    News & Views

  • Two studies show that specific cullin-RING E3 ubiquitin ligases can be targeted with small molecules.

    • John R Lydeard
    • J Wade Harper
    News & Views

  • Comprehensive phenotypic screening of knockout mice highlights the pleiotropic functions of secreted and transmembrane proteins.

    • Wolfgang Wurst
    • Martin Hrabe de Angelis
    News & Views

  • A comprehensive study identifies sequence features that predict tissue-specific alternative splicing.

    • Mauricio A Arias
    • Shengdong Ke
    • Lawrence A Chasin
    News & Views

  • The complete set of tools needed to synthesize a functional genome and transplant it into a mycoplasma cell opens up the possibility of mixing and matching natural and synthetic DNA to make genomes with new capabilities.

    • Mitsuhiro Itaya
    News & Views
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Research Highlights

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Commentary

  • Given the accumulation of DNA sequence data sets at ever-faster rates, what are the key factors you should consider when using distributed and multicore computing systems for analysis?

    • Michael C Schatz
    • Ben Langmead
    • Steven L Salzberg
    Commentary
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Perspective

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Letter

  • Live attenuated viruses make more effective vaccines than newer protein subunit or recombinant DNA vaccines, but the traditional passaging methods used to generate them often fail to produce a suitable mutant. Mueller et al. improve the production of live attenuated influenza virus by extensive manipulation of codon-pair bias across the genome, which minimizes the risk of reversion to a virulent form.

    • Steffen Mueller
    • J Robert Coleman
    • Eckard Wimmer
    Letter

  • Complex combinations of simultaneous stimuli control cellular responses, and cross-talk between signaling pathways makes it even more difficult to predict these responses. Chatterjee et al. demonstrate in human platelets that neural networks trained with measurements of pairwise stimuli can predict combinations of many signaling inputs.

    • Manash S Chatterjee
    • Jeremy E Purvis
    • Scott L Diamond
    Letter

  • Although general inhibitors of the ubiquitin-proteasome system have been reported, compounds targeting specific ubiquitylation enzymes should be beneficial in clinical applications and basic research. Orlicky et al. present an allosteric inhibitor specific to the yeast SCFCdc4 E3 ligase that prevents binding of the target protein to the WD40 domain of the complex.

    • Stephen Orlicky
    • Xiaojing Tang
    • Mike Tyers
    Letter

  • Although general inhibitors of the ubiquitin-proteasome system have been reported, compounds targeting specific ubiquitylation enzymes should be beneficial in clinical applications and basic research. Aghajan et al. present an inhibitor of the yeast SCFMet30 E3 ligase that prevents the binding of the Met30 F-box protein to the core ligase complex.

    • Mariam Aghajan
    • Nao Jonai
    • Jing Huang
    Letter

  • The ability to control the activity of cellular signaling pathways is useful for dissecting their functions. Using a short protein insert, Karginov et al. engineer protein kinases that can be specifically activated by the small-molecule rapamycin.

    • Andrei V Karginov
    • Feng Ding
    • Klaus M Hahn
    Letter
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Resource

  • Tang et al. present the first large-scale, gene-specific library of knockout mice. They disrupt 472 genes encoding secreted or transmembrane proteins and report the results of a comprehensive phenotypic analysis.

    • Tracy Tang
    • Li Li
    • Frederic J de Sauvage
    Resource
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Corrigendum

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Erratum

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Careers and Recruitment

  • Careers and Recruitment
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