Hepatic ERAD takes control of the organism.

Upregulation of Endoplasmic Reticulum‐Associated Degradation (ERAD) in the liver upon feeding and organismal growth aggravates proteasomal turnover of the transcription factor CREBH and decreases the expression of its target gene, the hepatokine FGF21. Wei and Bhattacharya describe the systemic coordination of energy metabolism and organismal physiology mediated by hepatic‐specific ERAD function.

ERADicate Tumor Progression with Metformin.

Endoplasmic reticulum-associated degradation (ERAD) plays a crucial role in turnover of defective secretory proteins to maintain protein homeostasis. Cha et al. (2018) revealed that the anti-diabetic drug metformin induces ERAD of programmed death ligand (PD-L1), which attenuates tumor growth.

Conserved cytoplasmic domains promote Hrd1 ubiquitin ligase complex formation for ER-associated degradation (ERAD).

The mammalian ubiquitin ligase Hrd1 is the central component of a complex facilitating degradation of misfolded proteins during the ubiquitin-proteasome-dependent process of ER-associated degradation (ERAD). Hrd1 associates with cofactors to execute ERAD, but their roles and how they assemble with Hrd1 are not well understood. Here, we identify crucial cofactor interaction domains within Hrd1 and report a previously unrecognised evolutionarily conserved segment within the intrinsically disordered cytoplasmic domain of Hrd1 (termed the HAF-H domain), which engages complementary segments in the cofactors FAM8A1 and Herp (also known as HERPUD1).