NFE2L1
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| Location (UCSC) | Chr 17: 48.05 – 48.06 Mb | Chr 11: 96.71 – 96.72 Mb | |||||||
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Nuclear factor erythroid 2-related factor 1 (Nrf1) also known as nuclear factor erythroid-2-like 1 (NFE2L1) is a protein that in humans is encoded by the NFE2L1 gene.[5][6][7] Since NFE2L1 is also referred to as Nrf1, it is often confused with nuclear respiratory factor 1.
NFE2L1 is a cap ‘n’ collar, basic-leucine zipper (bZIP) transcription factor. Several isoforms of NFE2L1 have been described for both human and mouse genes. NFE2L1 was first cloned in yeast using a genetic screening method. NFE2L1 is ubiquitously expressed, and high levels of transcript are detected in the heart, kidney, skeletal muscle, fat, and brain.[5] Four separate regions — an asparagine/serine/threonine, acidic domains near the N-terminus, and a serine-rich domain located near the CNC motif — are required for full transactivation function of NFE2L1.[8][9][10] NFE2L1 is a key regulator of cellular functions including oxidative stress response, differentiation, inflammatory response, metabolism, cholesterol handling[11] and maintaining proteostasis.
Interactions
NFE2L1 binds DNA as heterodimers with one of
Cellular homeostasis
NFE2L1 regulates a wide variety of cellular responses, several of which are related to important aspects of protection from stress stimuli. NFE2L1 is involved in providing cellular protection against oxidative stress through the induction of antioxidant genes. The
NFE2L1 is also involved in maintaining proteostasis. Brains of mice with conditional knockout of NFE2L1 in neuronal cells showed decreased proteasome activity and accumulation of ubiquitin-conjugated proteins, and down regulation of genes encoding the 20S core and 19S regulatory sub-complexes of the 26S proteasome.[22] A similar effect on proteasome gene expression and function was observed in livers of mice with NFE2L1 conditional knockout in hepatocytes.[23] Induction of proteasome genes was also lost in brains and livers of NFE2L1 conditional knockout mice. Re-establishment of NFE2L1 function in NFE2L1 null cells rescued proteasome expression and function, indicating NFE2L1 was necessary for induction of proteasome genes (bounce-back response) in response to proteasome inhibition.[24] This compensatory up-regulation of proteasome genes in response to proteasome inhibition has also been demonstrated to be NFE2L1-dependent in various other cell types.[25][26] NFE2L1 was shown to directly bind and activate expression of the PsmB6 gene, which encodes a catalytic subunit of the 20S core.[22][24] NFE2L1 was also shown to regulate expression of Herpud1 and Vcp/p97, which are components of the ER-associated degradation pathway.[27][26]
NFE2L1 also plays a role in metabolic processes. Loss of hepatic NFE2L1 has been shown to result in lipid accumulation, hepatocellular damage, cysteine accumulation, and altered fatty acid composition.
Regulation
NFE2L1 is an ER membrane protein. Its
Animal studies
Loss and gain of function studies in mice showed that dysregulation of NFE2L1 leads to pathological states that could have relevance in human diseases. NFE2L1 is crucial for embryonic development and survival of hepatocytes during development.
Notes
Wikidata Q38762571 . |
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000082641 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038615 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 8248256.
- ^ PMID 9501099.
- ^ "Entrez Gene: NFE2L1 nuclear factor (erythroid-derived 2)-like 1".
- S2CID 26136436.
- ^ PMID 18990090.
- ^ PMID 17609210.
- ^ PMID 29149604.
- PMID 9195958.
- PMID 9421508.
- PMID 9872330.
- PMID 18601945.
- PMID 10601325.
- PMID 11342101.
- PMID 15988009.
- ^ PMID 12808106.
- ^ PMID 15738389.
- PMID 18826952.
- ^ PMID 21536885.
- PMID 23702335.
- ^ PMID 20385086.
- ^ PMID 20932482.
- ^ PMID 24998528.
- S2CID 28176029.
- PMID 25092871.
- ^ PMID 25556857.
- S2CID 9281206.
- PMID 22971132.
- ]
- ^ PMID 21911472.
- PMID 24448410.
- PMID 21953459.
- PMID 23623971.
- PMID 23816881.
- PMID 15308669.
- PMID 20805060.
- PMID 16872277.
- PMID 22216197.
- PMID 26017155.
- PMID 25043031.
Further reading
- Zhang Y, Xiang Y (April 2016). "Molecular and cellular basis for the unique functioning of Nrf1, an indispensable transcription factor for maintaining cell homoeostasis and organ integrity". The Biochemical Journal. 473 (8): 961–1000. PMID 27060105.
- Yuan J, Zhang S, Zhang Y (September 2018). "Nrf1 is paved as a new strategic avenue to prevent and treat cancer, neurodegenerative and other diseases". Toxicology and Applied Pharmacology. 360: 273–283. S2CID 52890875.
- Luna L, Skammelsrud N, Johnsen O, Abel KJ, Weber BL, Prydz H, Kolstø AB (May 1995). "Structural organization and mapping of the human TCF11 gene". Genomics. 27 (2): 237–44. PMID 7557987.
- Luna L, Johnsen O, Skartlien AH, Pedeutour F, Turc-Carel C, Prydz H, Kolstø AB (Aug 1994). "Molecular cloning of a putative novel human bZIP transcription factor on chromosome 17q22". Genomics. 22 (3): 553–62. PMID 8001966.
- Caterina JJ, Donze D, Sun CW, Ciavatta DJ, Townes TM (Jun 1994). "Cloning and functional characterization of LCR-F1: a bZIP transcription factor that activates erythroid-specific, human globin gene expression". Nucleic Acids Research. 22 (12): 2383–91. PMID 8036168.
- Johnsen O, Skammelsrud N, Luna L, Nishizawa M, Prydz H, Kolstø AB (Nov 1996). "Small Maf proteins interact with the human transcription factor TCF11/Nrf1/LCR-F1". Nucleic Acids Research. 24 (21): 4289–97. PMID 8932385.
- Toki T, Itoh J, Kitazawa J, Arai K, Hatakeyama K, Akasaka J, Igarashi K, Nomura N, Yokoyama M, Yamamoto M, Ito E (Apr 1997). "Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif". Oncogene. 14 (16): 1901–10. PMID 9150357.
- Novotny V, Prieschl EE, Csonga R, Fabjani G, Baumruker T (Dec 1998). "Nrf1 in a complex with fosB, c-jun, junD and ATF2 forms the AP1 component at the TNF alpha promoter in stimulated mast cells". Nucleic Acids Research. 26 (23): 5480–5. PMID 9826775.
- Murphy P, Kolstø A (Oct 2000). "Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development". Mechanisms of Development. 97 (1–2): 141–8. S2CID 17474070.
- Jiang LQ, Wen SJ, Wang HY, Chen LY (Jul 2002). "Screening the proteins that interact with calpain in a human heart cDNA library using a yeast two-hybrid system". Hypertension Research. 25 (4): 647–52. PMID 12358155.
- Husberg C, Murphy P, Bjørgo E, Kalland KH, Kolstø AB (May 2003). "Cellular localisation and nuclear export of the human bZIP transcription factor TCF11". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1640 (2–3): 143–51. PMID 12729924.
- Newman JR, Keating AE (Jun 2003). "Comprehensive identification of human bZIP interactions with coiled-coil arrays". Science. 300 (5628): 2097–101. S2CID 36715183.
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. S2CID 4427026.
- Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC (Mar 2007). "Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects". Atherosclerosis. 191 (1): 63–72. PMID 16806233.
External links
- NFE2L1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.