Sec61β maintains cytoplasmic proteostasis via ARIH1-mediated translational repression upon ER stress

機関リポジトリ 機関リポジトリ (HANDLE) オープンアクセス

書誌事項

公開日
2026-01-27
資源種別
journal article
権利情報
  • © The Author(s)
公開者
Springer Science and Business Media LLC

説明

Disrupted proteostasis causes various degenerative diseases, and organelle homeostasis is therefore maintained by elaborate mechanisms. Endoplasmic reticulum (ER) stress-induced preemptive quality control (ERpQC) counteracts stress by reducing ER load through inhibiting the translocation of newly synthesized proteins into the ER for their rapid degradation in the cytoplasm. Here, we show that Sec61β, a translocon component, prevents the overproduction of ERpQC substrates, allowing for their efficient degradation by the proteasome. Sec61β inhibits the binding of translation initiation factor eIF4E to the mRNA 5' cap structure by recruiting E3 ligase ARIH1 and eIF4E-homologous protein 4EHP, resulting in selective translational repression of ERpQC substrates. Sec61β deficiency causes overproduction of ERpQC substrates and reduces proteasome activity, leading to cytoplasmic aggresome formation. We also show that Sec61β deficiency causes motor dysfunction in zebrafish, which is restored by exogenous ARIH1 expression. Collectively, translational repression of ERpQC substrates by the Sec61β-ARIH1 complex contributes to maintain ER and cytoplasmic proteostasis.

収録刊行物

  • EMBO reports

    EMBO reports 2026-01-27

    Springer Science and Business Media LLC

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