Regulation of the ER-bound transcription factor Luman/CREB3 in HEK293 cells

FEBS Letters

article

Kentaro Oh-hashi¹  Kanto Takahashi²  Yoko Hirata¹ 

[1] United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University;Graduate School of Natural Science and Technology, Gifu University;Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University

关键词: CREB3;    ERAD;    Herp;    SEL1L;   

DOI  :  10.1002/1873-3468.13535

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 ERassociated 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 amannosidase 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.

【 授权许可】

Unknown