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

Publication ,  Journal Article
Sun, S; Shi, G; Han, X; Francisco, AB; Ji, Y; Mendonça, N; Liu, X; Locasale, JW; Simpson, KW; Duhamel, GE; Kersten, S; Yates, JR; Long, Q; Qi, L
Published in: Proc Natl Acad Sci U S A
February 4, 2014

Suppressor/Enhancer of Lin-12-like (Sel1L) is an adaptor protein for the E3 ligase hydroxymethylglutaryl reductase degradation protein 1 (Hrd1) involved in endoplasmic reticulum-associated degradation (ERAD). Sel1L's physiological importance in mammalian ERAD, however, remains to be established. Here, using the inducible Sel1L knockout mouse and cell models, we show that Sel1L is indispensable for Hrd1 stability, ER homeostasis, and survival. Acute loss of Sel1L leads to premature death in adult mice within 3 wk 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 a 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 the mammalian Hrd1 ERAD complex and ER homeostasis, which is essential for protein translation, pancreatic function, and cellular and organismal survival.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 4, 2014

Volume

111

Issue

5

Start / End Page

E582 / E591

Location

United States

Related Subject Headings

  • Unfolded Protein Response
  • Ubiquitin-Protein Ligases
  • Secretory Vesicles
  • Proteins
  • Protein Stability
  • Protein Biosynthesis
  • Polyribosomes
  • Pancreas, Exocrine
  • Models, Biological
  • Mice, Knockout
 

Citation

APA
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Sun, S., Shi, G., Han, X., Francisco, A. B., Ji, Y., Mendonça, N., … Qi, L. (2014). Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival. Proc Natl Acad Sci U S A, 111(5), E582–E591. https://doi.org/10.1073/pnas.1318114111
Sun, Shengyi, Guojun Shi, Xuemei Han, Adam B. Francisco, Yewei Ji, Nuno Mendonça, Xiaojing Liu, et al. “Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival.Proc Natl Acad Sci U S A 111, no. 5 (February 4, 2014): E582–91. https://doi.org/10.1073/pnas.1318114111.
Sun S, Shi G, Han X, Francisco AB, Ji Y, Mendonça N, et al. Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival. Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):E582–91.
Sun, Shengyi, et al. “Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival.Proc Natl Acad Sci U S A, vol. 111, no. 5, Feb. 2014, pp. E582–91. Pubmed, doi:10.1073/pnas.1318114111.
Sun S, Shi G, Han X, Francisco AB, Ji Y, Mendonça N, Liu X, Locasale JW, Simpson KW, Duhamel GE, Kersten S, Yates JR, Long Q, Qi L. Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival. Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):E582–E591.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 4, 2014

Volume

111

Issue

5

Start / End Page

E582 / E591

Location

United States

Related Subject Headings

  • Unfolded Protein Response
  • Ubiquitin-Protein Ligases
  • Secretory Vesicles
  • Proteins
  • Protein Stability
  • Protein Biosynthesis
  • Polyribosomes
  • Pancreas, Exocrine
  • Models, Biological
  • Mice, Knockout