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Journal of Shanghai University >

2021 , Vol. 27 >Issue 3: 563 - 572

DOI: https://doi.org/10.12066/j.issn.1007-2861.2142

Research Articles

MEK5$\alpha $ and MEK5$\beta $ differentially regulate Beclin 1 promoter

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  • Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai JiaoTong University, Shanghai 200240, China

Received date: 2019-03-27

  Online published: 2019-05-28

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Abstract

Beclin 1, a mammalian autophagy-related gene, regulates autophagy initiation and autophagosome maturation. During muscle differentiation, Beclin 1 is upregulated. Additionally, MEK5-ERK5 is activated to regulate muscle differentiation. Thus, MEK5-ERK5 may regulate Beclin 1 gene expression during muscle differentiation. The aim of this study was to determine MEK5 regulation of Beclin 1 promoter in myoblast cells. A series of promoter-luciferase constructs harbouring different lengths of Beclin 1 promoter were created and transfected into myoblast C2C12 cells. In the luciferase assay, the construct containing 586 base pairs upstream of the start codon (p-354) exhibited the most potent luciferase activity. MEK5$\alpha $ and MEK5$\beta $ enhanced and suppressed p-354 luciferase activity, respectively. MEK5$\beta $ is capable of antagonizing the effect of MEK5$\alpha $ on p-354 luciferase activity. Consistent with the results on the regulatory effects of MEK5 on Beclin 1 promoter, MEK5$\alpha $CA and MEK5$\beta $DD upregulated and downregulated Beclin 1 mRNA expression, respectively. Moreover, MEK5$\beta $DD antagonised the stimulatory effects of MEK5$\alpha $CA on Beclin 1 mRNA expression. Members of the CREB family, including CREB3, CREBP, and CREBL1, promoted p-354 luciferase activity. Furthermore, CREB3 dose-dependently increased p-354 luciferase activity and exhibited a synergistic effect with MEK5$\alpha $ on p-354 luciferase activity. Collectively, these findings indicate that MEK5$\alpha $ and MEK5$\beta $ differentially regulate Beclin 1 promoter activity and that CREB family members may be downstream effectors.

Key words： MEK5; Beclin 1; promoter; luciferase reporter gene

Cite this article

LIU Xiaoyun, WANG Leibin, WANG Qing, ZHANG Shasha, ZHAO Weimiao, HE Lin, ZHU Hongxin . MEK5$\alpha $ and MEK5$\beta $ differentially regulate Beclin 1 promoter[J]. Journal of Shanghai University, 2021 , 27(3) : 563 -572 . DOI: 10.12066/j.issn.1007-2861.2142

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