MAFF (gene)
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| Location (UCSC) | Chr 22: 38.2 – 38.22 Mb | Chr 15: 79.23 – 79.24 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Transcription factor MafF is a bZip Maf transcription factor protein that in humans is encoded by the MAFF gene.[5][6]
MafF is one of the small Maf proteins, which are basic region and leucine zipper (bZIP)-type transcription factors. The HUGO Gene Nomenclature Committee-approved gene name of MAFF is “v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F”.
Discovery
MafF was first cloned and identified in chicken in 1993 as a member of the small Maf (sMaf) genes.[5] MAFF has been identified in many vertebrates, including humans.[6] There are three functionally redundant sMaf proteins in vertebrates, MafF, MafG, and MafK.
Structure
MafF has a bZIP structure that consists of a basic region for DNA binding and a leucine zipper structure for dimer formation.[5] Similar to other sMafs, MafF lacks any canonical transcriptional activation domains.[5]
Expression
MAFF is broadly but differentially expressed in various tissues. MAFF expression was detected in all 16 tissues examined by the human BodyMap Project, but relatively abundant in adipose, colon, lung, prostate and skeletal muscle tissues.[7] Human MAFF gene is induced by proinflammatory cytokines, interleukin 1 beta and tumor necrosis factor in myometrial cells.[8]
Function
Because of sequence similarity, no functional differences have been observed among the sMafs in terms of their bZIP structures. sMafs form homodimers by themselves and heterodimers with other specific bZIP transcription factors, such as CNC (cap 'n' collar) proteins [p45 NF-E2 (NFE2), Nrf1 (NFE2L1), Nrf2 (NFE2L2), and Nrf3 (NFE2L3)][9][10][11][12] and Bach proteins (BACH1 and BACH2).[13]
Target genes
sMafs regulate different target genes depending on their partners. For instance, the p45-NF-E2-sMaf heterodimer regulate genes responsible for platelet production.[9][14][15] Nrf2-sMaf heterodimer regulates a battery of cytoprotective genes, such as antioxidant/xenobiotic metabolizing enzyme genes.[11][16] The Bach1-sMaf heterodimer regulates the heme oxygenase-1 gene.[13] In particular, it has been reported that MafF regulates the oxytocin receptor gene.[17] The contribution of individual sMafs to the transcriptional regulation of their target genes has not yet been well examined.
Disease linkage
Loss of sMafs results in disease-like phenotypes as summarized in table below. Mice lacking MafF are seemingly healthy under laboratory conditions.[18] However, mice lacking MafG exhibit mild neuronal phenotype and mild thrombocytopenia,[19] mice lacking Mafg and one allele of Mafk (Mafg−/−::Mafk+/−) exhibit progressive neuronal degeneration, thrombocytopenia and cataract,[20][21] and mice lacking MafG and MafK (Mafg−/−::Mafk−/−) exhibit more severe neuronal degeneration and die in the perinatal stage.[22] Mice lacking MafF, MafG and MafK are embryonic lethal, demonstrating that MafF is indispensable for embryonic development.[23] Embryonic fibroblasts that are derived from Maff−/−::Mafg-/−::Mafk−/− mice fail to activate Nrf2-dependent cytoprotective genes in response to stress.[16]
| Genotype | Mouse Phenotype | ||
|---|---|---|---|
| Maff | Mafg | Mafk | |
| −/− | No apparent phenotype under laboratory conditions [18] | ||
| −/− | Mild motor ataxia, mild thrombocytopenia [19] | ||
| −/− | +/− | Severe motor ataxia, progressive neuronal degeneration, severe thrombocytopenia, and cataract [20][21] | |
| −/− | −/− | More severe neuronal phenotypes, and perinatal lethal [22] | |
| −/− | +/− | −/− | No severe abnormality [23] (Fertile) |
| −/− | −/− | −/− | Growth retardation, fetal liver hypoplasia, and lethal around embryonic day, 13.5 [23] |
| +/− ( homozygote ), blank (wild-type)
| |||
In addition, accumulating evidence suggests that as partners of CNC and Bach proteins, sMafs are involved in the onset and progression of various human diseases, including neurodegeneration, arteriosclerosis and cancer.
See also
Notes
Wikidata Q37014084 . |
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000185022 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042622 – 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 8361754.
- ^ a b "Entrez Gene: MAFF v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (avian)".
- PMID 24304889.
- S2CID 11823930.
- ^ S2CID 4339431.
- PMID 9421508.
- ^ PMID 9240432.
- PMID 10037736.
- ^ PMID 8887638.
- PMID 9679061.
- S2CID 14195541.
- ^ PMID 16135796.
- PMID 10527846.
- ^ PMID 10409670.
- ^ PMID 9679061.
- ^ PMID 12556477.
- ^ PMID 25896808.
- ^ PMID 10716933.
- ^ PMID 22158967.
Further reading
- Ye X, Li Y, Huang Q, Yu Y, Yuan H, Wang P, Wan D, Gu J, Huo K, Li YY, Lu H (May 2006). "The novel human gene MIP functions as a co-activator of hMafF". Archives of Biochemistry and Biophysics. 449 (1–2): 87–93. PMID 16549056.
- Massrieh W, Derjuga A, Doualla-Bell F, Ku CY, Sanborn BM, Blank V (Apr 2006). "Regulation of the MAFF transcription factor by proinflammatory cytokines in myometrial cells". Biology of Reproduction. 74 (4): 699–705. S2CID 11823930.
- Marini MG, Asunis I, Chan K, Chan JY, Kan YW, Porcu L, Cao A, Moi P (2003). "Cloning MafF by recognition site screening with the NFE2 tandem repeat of HS2: analysis of its role in globin and GCSl genes regulation". Blood Cells, Molecules & Diseases. 29 (2): 145–58. PMID 12490281.
- Moran JA, Dahl EL, Mulcahy RT (Jan 2002). "Differential induction of mafF, mafG and mafK expression by electrophile-response-element activators". The Biochemical Journal. 361 (Pt 2): 371–7. PMID 11772409.
- Kataoka K, Yoshitomo-Nakagawa K, Shioda S, Nishizawa M (Jan 2001). "A set of Hox proteins interact with the Maf oncoprotein to inhibit its DNA binding, transactivation, and transforming activities". The Journal of Biological Chemistry. 276 (1): 819–26. PMID 11036080.
- Kimura T, Ivell R, Rust W, Mizumoto Y, Ogita K, Kusui C, Matsumura Y, Azuma C, Murata Y (Oct 1999). "Molecular cloning of a human MafF homologue, which specifically binds to the oxytocin receptor gene in term myometrium". Biochemical and Biophysical Research Communications. 264 (1): 86–92. PMID 10527846.
- 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.
- Igarashi K, Kataoka K, Itoh K, Hayashi N, Nishizawa M, Yamamoto M (Feb 1994). "Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins". Nature. 367 (6463): 568–72. S2CID 4339431.
External links
- MAFF+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- FactorBook MafF