E-GEOD-52929 - Sel1L is Indispensable for Mammalian ERAD, ER Homeostasis and Survival
Released on 4 December 2013, last updated on 3 June 2014
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. Pancreas tissue of wild type and inducible Sel1L knockout mice were subjected to gene expression analysis.
transcription profiling by array
Guido Hooiveld <email@example.com>, Adam B Francisco, Gerald Duhamel, Guojun Shi, Jason W Locasale, John R Yates III, Kenneth W Simpson, Ling Qi, Nuno Mendonça, Qiaoming Long, Sander Kersten, Shengyi Sun, Xiaojing Liu, Xuemei Han, Yewei Ji