Small Interfering Peptide (siP) for In Vivo Examination of the Developing Lung Interactonome

J. Craig Cohen, Erin Killeen, Avinash Chander, Ken-Ichi Takemaru, Janet E. Larson, Kate J. Treharne, Anil Mehta

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    6 Citations (Scopus)

    Abstract

    approach to interfere with protein-protein interactions by means of a short interacting peptide was developed. This technology was used in the developing rodent lung to examine the role of NADPH oxidase (NOX), casein kinase 2 (CK2), and the cystic fibrosis transmembrane conductance regulator (CFTR) in stretch-induced differentiation. Interactions between these molecules was targeted in an in utero system with recombinant adeno-associated virus (rAAV) containing inserted DNA sequences that express a control peptide or small interfering peptides (siPs) specific for subunit interaction or phosphorylation predicted to be necessary for multimeric enzyme formation. In all cases only siPs with sequences necessary for a predicted normal function were found to interfere with assembly of the multimeric enzyme. A noninterfering control siP to nonessential regions or reporter genes alone had no effect. Physiologically, it was shown that siPs that interfered with the NOX-CFTR-CK2 complex that we call an "interactonome" affected markers of stretch-induced lung organogenesis including Wnt/beta-catenin signaling. Developmental Dynamics 238:386-393, 2009. (c) 2009 Wiley-Liss, Inc.

    Original languageEnglish
    Pages (from-to)386-393
    Number of pages8
    JournalDevelopmental Dynamics
    Volume238
    Issue number2
    DOIs
    Publication statusPublished - Feb 2009

    Keywords

    • NADPH oxidase
    • casein kinase 2
    • myosin light chain phosphorylation
    • lung development
    • Wnt/beta-catenin signaling
    • stretch-induced differentiation
    • TRANSMEMBRANE CONDUCTANCE REGULATOR
    • HORMONE-RELATED PROTEIN
    • OXIDASE ACTIVITY
    • NADPH OXIDASE
    • GENE-TRANSFER
    • HOST-DEFENSE
    • CFTR
    • MODULATION
    • MUSCLE
    • ACTIN

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