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• W2065544945 endingPage "3210" @default.
• W2065544945 startingPage "3195" @default.
• W2065544945 abstract "Transcription factor Nrf3 (NF-E2 p45-related factor 3) is targeted to the endoplasmic reticulum (ER). Mouse Nrf3 is subject to proteolysis, Asn glycosylation, and deglycosylation reactions. It is synthesized as a ∼96-kDa protein that is subsequently converted into isoforms of ∼90, 80, and 70 kDa. In the ER, the ∼90-kDa glycoprotein is predominant and gives rise to ∼80- and ∼70-kDa isoforms. The ∼90- and ∼80-kDa polypeptides were observed in the nuclear envelope, whereas the ∼70-kDa isoform was detected primarily in the nucleoplasm. Our experiments showed the N-terminal homology box 1 (NHB1, residues 12-31) is part of a tripartite signal peptide sequence, comprising n, h, and c regions. The h region (residues 12-23) was demonstrated to target Nrf3 to the ER and is necessary for its Asn glycosylation. The n region (residues 1-11) controlled the abundance of the ∼90-kDa glycoprotein. The c region (residues 24-39) was found to contain a signal peptidase cleavage site that is responsible for production of the ∼90-kDa mature Nrf3 glycoprotein from a ∼96-kDa precursor. We have found that Nrf3 is activated by the ER stressors tunicamycin and brefeldin A, and that NHB1 is required for this response. Amino acids between the c region and NHB2 (residues 76-100) controlled the proteolytic processing of mouse Nrf3 into cleavage products of ∼80-kDa (glycated) and ∼70-kDa (non-glycated); by contrast, human Nrf3 lacked a signal peptidase cleavage site between its c region and NHB2. Lastly, data are presented suggesting that the NHB2 sequence in mouse Nrf3 may regulate the topology of the transcription factor within the ER membrane." @default.
• W2065544945 created "2016-06-24" @default.
• W2065544945 creator A5019212356 @default.
• W2065544945 creator A5046024649 @default.
• W2065544945 creator A5049582015 @default.
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• W2065544945 date "2009-01-01" @default.
• W2065544945 modified "2023-10-16" @default.
• W2065544945 title "The Nrf3 Transcription Factor Is a Membrane-bound Glycoprotein Targeted to the Endoplasmic Reticulum through Its N-terminal Homology Box 1 Sequence" @default.
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• W2065544945 doi "https://doi.org/10.1074/jbc.m805337200" @default.
• W2065544945 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19047052" @default.
• W2065544945 hasPublicationYear "2009" @default.
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