Abstract: Objective To investigate the effect of sterol regulating element binding protein (SREBP1c) and its active form (SREBP1cm) on human protein kinase R-like endoplasmic reticulum kinase (PERK). Methods Reporter victors of PERK promoter and its truncations are constructed with pGL3-basic and co-transfected with internal reference pRL-SV40 into cell and luciferase activity was detected. pcDNA3.1(-)-SREBP1c or pcDNA3.1(-)-SREBP1cm was co-transfected with PERK promoter transcriptional activity core regions and the detection of dual-luciferase reporter gene was used to analyze the regulation of SREBP1c/1cm on PERK promoter transcriptional activity. The expression level of PERK mRNA and protein were detected by RT-PCR and Western blot. Results PERK promoter and truncations were successfully constructed into pGL3-basic, and PERK promoter core area of transcriptional activity had determined; Dual-luciferase report gene showed that SREBP1c inhibits PERK promoter transcriptional activity and SREBP1cm promotes PERK promoter transcriptional activity. RT-PCR and Western blot showed that SREBP1c decreased PERK mRNA and protein expression, but SREBP1cm increased PERK mRNA and protein expression, which was consistent with the detection of dual-luciferase report gene. Conclusions SREBP1c and SREBP1cm have a opposite regulation effect on PERK promoter transcriptional activity and its expression.

Key words: PERK, SREBP1c, Transcriptional activity, ER stress