Importin beta Interacts with the Endoplasmic Reticulum-associated Degradation Machinery and Promotes Ubiquitination and Degradation of Mutant alpha 1-Antitrypsin

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ZHONG Y., WANG Y., YANG H., Ballar P. , LEE J., YE Y., ...Daha Fazla

JOURNAL OF BIOLOGICAL CHEMISTRY, cilt.286, ss.33921-33930, 2011 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 286 Konu: 39
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1074/jbc.m111.272906
  • Sayfa Sayıları: ss.33921-33930


The mechanism by which misfolded proteins in the endoplasmic reticulum (ER) are retrotranslocated to the cytosol for proteasomal degradation is still poorly understood. Here, we show that importin beta, a well established nucleocytoplasmic transport protein, interacts with components of the retrotranslocation complex and promotes ER-associated degradation (ERAD). Knockdown of importin beta specifically inhibited the degradation of misfolded ERAD substrates but did not affect turnover of non-ERAD proteasome substrates. Genetic studies and in vitro reconstitution assays demonstrate that importin beta is critically required for ubiquitination of mutant beta 1-antitrypsin, a luminal ERAD substrate. Furthermore, we show that importin beta cooperates with Ran GTPase to promote ubiquitination and proteasomal degradation of mutant beta 1-antitrypsin. These results establish an unanticipated role for importin beta in ER protein quality control.