Alterations of EDEM1 functions enhance ATF6 pro-survival signaling - Archive ouverte HAL Access content directly
Journal Articles FEBS Journal Year : 2018

Alterations of EDEM1 functions enhance ATF6 pro-survival signaling


Activating transcription factor 6 alpha (referred to as ATF6 hereafter) is an endoplasmic reticulum (ER)-resident glycoprotein and one of the three sensors of the unfolded protein response (UPR). Upon ER stress, ATF6 is exported to the Golgi complex where it is cleaved by the S1P and S2P proteases thus releasing ATF6 cytosolic fragment and leading to the transcription of ATF6 target genes. In this study, we performed a phenotypic small-interfering RNA (siRNA) screening to better characterize the ER mechanisms involved in ATF6 activation upon ER stress. This revealed that silencing of ER-degradation-enhancing alpha-mannosidase-like protein-1 (EDEM1) increased the bioavailability of ER stress-induced ATF6 export to the Golgi complex through the stabilization of the natively unstable ATF6 protein. Moreover, we characterized a somatic variant of EDEM1 (N198I) found in hepatocellular carcinoma that alters ATF6 signaling and might provide a selective advantage to the transforming cells. Hence, our work confirms the natively unstable nature of ATF6 and links this property to potentially associated pro-oncogenic functions.
Fichier principal
Vignette du fichier
Papaioannou et al_Alterations of EDEM1 functions enhance ATF6 pro-survival signaling.pdf (2.12 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-01940302 , version 1 (14-12-2018)



Alexandra Papaioannou, Arisa Higa, Gwenaele Jegou, Florence Jouan, Raphael Pineau, et al.. Alterations of EDEM1 functions enhance ATF6 pro-survival signaling. FEBS Journal, 2018, 285 (22), pp.4146-4164. ⟨10.1111/febs.14669⟩. ⟨hal-01940302⟩
62 View
92 Download



Gmail Facebook Twitter LinkedIn More