| First Author | Zhang Y | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 5 | Pages | 3195-210 |
| PubMed ID | 19047052 | Mgi Jnum | J:147221 |
| Mgi Id | MGI:3839708 | Doi | 10.1074/jbc.M805337200 |
| Citation | Zhang Y, et al. (2009) The Nrf3 transcription factor is a membrane-bound glycoprotein targeted to the endoplasmic reticulum through its N-terminal homology box 1 sequence. J Biol Chem 284(5):3195-210 |
| abstractText | 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 approximately 96-kDa protein that is subsequently converted into isoforms of approximately 90, 80, and 70 kDa. In the ER, the approximately 90-kDa glycoprotein is predominant and gives rise to approximately 80- and approximately 70-kDa isoforms. The approximately 90- and approximately 80-kDa polypeptides were observed in the nuclear envelope, whereas the approximately 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 approximately 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 approximately 90-kDa mature Nrf3 glycoprotein from a approximately 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 approximately 80-kDa (glycated) and approximately 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. |
