Peripheral protein quality control removes unfolded CFTR from the plasma membrane

Tsukasa Okiyoneda, Hervé Barrière, Miklós Bagdány, Wael Rabeh, Kai Du, Jörg Höhfeld, Jason C. Young, Gergely L. Lukacs

    Research output: Contribution to journalArticle

    Abstract

    Therapeutic efforts to restore biosynthetic processing of the cystic fibrosis transmembrane conductance regulator lacking the F508 residue (ΔF508CFTR) are hampered by ubiquitin-dependent lysosomal degradation of nonnative, rescued ΔF508CFTR from the plasma membrane. Here, functional small interfering RNA screens revealed the contribution of chaperones, cochaperones, and ubiquitin-conjugating and -ligating enzymes to the elimination of unfolded CFTR from the cell surface, as part of a peripheral protein quality-control system. Ubiquitination of nonnative CFTR was required for efficient internalization and lysosomal degradation. This peripheral protein quality-control mechanism probably participates in the preservation of cellular homeostasis by degrading damaged plasma membrane proteins that have escaped from the endoplasmic reticulum quality control or are generated by environmental stresses in situ.

    Original languageEnglish (US)
    Pages (from-to)805-810
    Number of pages6
    JournalScience
    Volume329
    Issue number5993
    DOIs
    StatePublished - Aug 13 2010

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    Quality Control
    Cell Membrane
    Ubiquitin-Conjugating Enzymes
    Cystic Fibrosis Transmembrane Conductance Regulator
    Proteins
    Ubiquitination
    Ubiquitin
    Endoplasmic Reticulum
    Small Interfering RNA
    Blood Proteins
    Membrane Proteins
    Homeostasis
    Therapeutics

    ASJC Scopus subject areas

    • General

    Cite this

    Okiyoneda, T., Barrière, H., Bagdány, M., Rabeh, W., Du, K., Höhfeld, J., ... Lukacs, G. L. (2010). Peripheral protein quality control removes unfolded CFTR from the plasma membrane. Science, 329(5993), 805-810. https://doi.org/10.1126/science.1191542

    Peripheral protein quality control removes unfolded CFTR from the plasma membrane. / Okiyoneda, Tsukasa; Barrière, Hervé; Bagdány, Miklós; Rabeh, Wael; Du, Kai; Höhfeld, Jörg; Young, Jason C.; Lukacs, Gergely L.

    In: Science, Vol. 329, No. 5993, 13.08.2010, p. 805-810.

    Research output: Contribution to journalArticle

    Okiyoneda, T, Barrière, H, Bagdány, M, Rabeh, W, Du, K, Höhfeld, J, Young, JC & Lukacs, GL 2010, 'Peripheral protein quality control removes unfolded CFTR from the plasma membrane', Science, vol. 329, no. 5993, pp. 805-810. https://doi.org/10.1126/science.1191542
    Okiyoneda T, Barrière H, Bagdány M, Rabeh W, Du K, Höhfeld J et al. Peripheral protein quality control removes unfolded CFTR from the plasma membrane. Science. 2010 Aug 13;329(5993):805-810. https://doi.org/10.1126/science.1191542
    Okiyoneda, Tsukasa ; Barrière, Hervé ; Bagdány, Miklós ; Rabeh, Wael ; Du, Kai ; Höhfeld, Jörg ; Young, Jason C. ; Lukacs, Gergely L. / Peripheral protein quality control removes unfolded CFTR from the plasma membrane. In: Science. 2010 ; Vol. 329, No. 5993. pp. 805-810.
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