Abstract
Usually, secreted or transmembrane proteins complete their three-dimension folding within endoplasmic reticulum (ER). Under the conditions of nutrient depletion, cell differentiation, or other stress statuses, misfolded or unfolded proteins aggregate within ER, and consequently cause ER stress and Unfolded Protein Response (UPR). In response to ER stress, BiP (Binding immunoglobulin protein) dissociates with IRE1a (Inositol-requiring kinase 1) and binds to unfolded proteins as a molecular chaperone in helping maintain their correct structure. Co-related to BiP's dissociation, IRE1a oglimerizes and activated its endoribonuclease domain by transautophosphorylation. Activated IRE1a then, by cleaving mRNA of Xbp1 and activating its transcription activity, triggers UPR. In this paper, in order to determine effect of BiP on transcription activity of IRE1a, we cloned promoter region of IRE1a into reporter gene analysis vector and found that BiP could upregulate promoter activity of IRE1a. Then, we constructed another 6 truncated promoter reporter vectors of IRE1a and pinpoint the core promoter activity region. Furthermore, both our RT-PCR and Western blot results showed that BiP could upregulate mRNA transcription level and protein expression level of IRE1a. Base on these findings, we can propose that, in order to alleviate ER stress caused by the misfolded or malfolded proteins, BiP could upregulate expression of IRE1a by increase its promoter activity. This study may suggest a novel signal pathway on IRE1a regulation in ER stress.
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