Sel1L is Indispensable for Mammalian ERAD, ER Homeostasis and Survival

  • Shengyi Sun (Creator)
  • Guojun Shi (Creator)
  • Xuemei Han (Creator)
  • Adam B. Francisco (Creator)
  • Yewei Ji (Creator)
  • Nuno Mendonça (Creator)
  • Xiaojing Liu (Creator)
  • Jason W. Locasale (Creator)
  • Kenneth W. Simpson (Creator)
  • Gerald Duhamel (Creator)
  • Sander Kersten (Creator)
  • John R. Yates III (Creator)
  • Qiaoming Long (Creator)
  • Ling Qi (Creator)

Dataset

Description

Sel1L is an adaptor protein for the E3 ligase Hrd1 involved in endoplasmic reticulum-associated degradation (ERAD). Its physiological importance in mammalian ERAD, however, remains to be established. Here, using the inducible Sel1L knockout mouse and cell models, we provide the first in vivo evidence that Sel1L is indispensable for Hrd1 stability, ER homeostasis and survival. Acute loss of Sel1L leads to premature death in adult mice within 3 weeks with profound pancreatic atrophy. Contrary to current belief, our data show that mammalian Sel1L is required for Hrd1 stability and ERAD function both in vitro and in vivo. Sel1L deficiency disturbs ER homeostasis, activates ER stress, attenuates translation and promotes cell death. Serendipitously, using biochemical approach coupled with mass spectrometry, we found that Sel1L deficiency causes the aggregation of both small and large ribosomal subunits. Thus, Sel1L is an indispensable component of mammalian ERAD and ER homeostasis, which is essential for protein translation, pancreatic function, cellular and organismal survival.
Date made available4 Dec 2013
PublisherWageningen University

Research Output

Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival

Sun, S., Shi, G., Han, X., Francisco, A., Ji, Y. & Kersten, A. H., 2014, In : Proceedings of the National Academy of Sciences of the United States of America. 111, 5, p. E582-E591

Research output: Contribution to journalArticleAcademicpeer-review

Open Access
  • 67 Citations (Scopus)

    Cite this

    Sun, S. (Creator), Shi, G. (Creator), Han, X. (Creator), Francisco, A. B. (Creator), Ji, Y. (Creator), Mendonça, N. (Creator), Liu, X. (Creator), Locasale, J. W. (Creator), Simpson, K. W. (Creator), Duhamel, G. (Creator), Kersten, S. (Creator), Yates III, J. R. (Creator), Long, Q. (Creator), Qi, L. (Creator) (4 Dec 2013). Sel1L is Indispensable for Mammalian ERAD, ER Homeostasis and Survival. Wageningen University.