Peripheral protein quality control removes unfolded CFTR from the plasma membrane

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

Research output: Contribution to journalArticlepeer-review


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
Issue number5993
StatePublished - Aug 13 2010

ASJC Scopus subject areas

  • General


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