Regulation of the ER‐bound transcription factor Luman/CREB3 in HEK293 cells. Issue 19 (21st July 2019)

• Record Type: Journal Article
• Authors: Oh‐hashi, Kentaro; Takahashi, Kanto; Hirata, Yoko
• Is Part Of: FEBS letters. Volume 593:Issue 19(2019)
• Page Start: 2771
• Page End: 2778
• Publication Date: 2019-07-21
• Subjects: CREB3 -- ERAD -- Herp -- SEL1L; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13535
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : CREB3 is a transcription factor localized to the ER. Here, we investigated endogenous CREB3 expression in HEK293 cells using pharmacological and genome editing approaches. Full‐length CREB3 detected under resting conditions disappeared following treatment with tunicamycin, brefeldin A and nigericin. Treatment with cycloheximide and MG132 indicated that endogenous CREB3 is a proteasome substrate. Using cells deficient for the ER‐associated protein degradation (ERAD) factors SEL1L and Herp, we demonstrate that SEL1L, but not Herp, plays a crucial role in the posttranslational regulation of full‐length CREB3 expression. In addition, kifunensine, an α‐mannosidase inhibitor, remarkably increased full‐length CREB3 expression. Our study suggests that endogenous full‐length CREB3 is a novel substrate for ERAD and identifies unique cellular signals distinct from those in canonical ER stress. Abstract :