MAFK

See also: Small Maf
V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog K
Identifiers
Symbols MAFK ; NFE2U; P18
External IDs OMIM: 600197 MGI: 99951 HomoloGene: 1770 GeneCards: MAFK Gene
Orthologs
Species Human Mouse
Entrez 7975 17135
Ensembl ENSG00000198517 ENSMUSG00000018143
UniProt O60675 Q61827
RefSeq (mRNA) NM_002360 NM_010757
RefSeq (protein) NP_002351 NP_034887
Location (UCSC) Chr 7:
1.53 – 1.54 Mb		 Chr 5:
139.79 – 139.8 Mb
PubMed search

Transcription factor MafK is a bZip Maf transcription factor protein that in humans is encoded by the MAFK gene.[1][2]

MafK is one of the small Maf proteins, which are basic region and basic leucine zipper (bZIP)-type transcription factors. The HUGO Gene Nomenclature Committee-approved gene name of MAFK is “v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog K”.

Discovery

MafK was first cloned and identified in chicken in 1993 as a member of the small Maf (sMaf) genes. MafK was also identified as p18 NF-E2, a component of NF-E2 complex binding to a specific motif (NF-E2) in the regulatory regions of β-globin and other erythroid-related genes.[3] MAFK has been identified in many vertebrates, including humans. There are three functionally redundant sMaf proteins in vertebrates, MafF, MafG, and MafK.[2]

Structure

MafK has a bZIP structure that consists of a basic region for DNA binding and a leucine zipper structure for dimer formation.[1] Similar to other sMafs, MafK lacks any canonical transcriptional activation domains.[1]

Expression

MAFK is broadly but differentially expressed in various tissues. MAFK expression was detected in all 16 tissues examined by the human BodyMap Project, but relatively abundant in adipose, lung and skeletal muscle tissues.[4] Mouse Mafk is regulated by different GATA factors in both hematopoietic and cardiac tissues.[5] MAFK expression is influenced by TGF-β[6] and Wnt signaling,[7] and rat Mafk expression is influenced by NGF[8] and AKT[9] in neuronal cells.

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)][10][11][12][13] and Bach proteins (BACH1 and BACH2).[14]

sMaf homodimers bind to a palindromic DNA sequence called the Maf recognition element (MARE: TGCTGACTCAGCA) and its related sequences.[1][15] Structural analyses have demonstrated that the basic region of a Maf factor recognizes the flanking GC sequences.[16] By contrast, CNC-sMaf or Bach-sMaf heterodimers preferentially bind to DNA sequences (RTGA(C/G)NNNGC: R=A or G) that are slightly different from MARE.[17] The latter DNA sequences have been recognized as antioxidant/electrophile response elements[18][19] or NF-E2-binding motifs[20][21] to which Nrf2-sMaf heterodimers and p45 NF-E2-sMaf heterodimer bind, respectively. It has been proposed that the latter sequences should be classified as CNC-sMaf-binding elements (CsMBEs).[17]

It has also been reported that sMafs form heterodimers with other bZIP transcription factors, such as c-Jun and c-Fos.[22]

Target genes

sMafs regulate different target genes depending on their partners. For instance, the p45-NF-E2-sMaf heterodimer regulates genes responsible for platelet production.[10][23][24] Although it has not been confirmed by mouse genetic studies, many studies suggest that p45-NFE2-sMaf heterodimer is involved in the regulation of β-globin and other erythroid-related genes.[3][10] Nrf2-sMaf heterodimer regulates a battery of cytoprotective genes, such as antioxidant/xenobiotic metabolizing enzyme genes.[12][25] The Bach1-sMaf heterodimer regulates the heme oxygenase-1 gene.[14] 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 MafK are seemingly healthy under laboratory conditions,[23] while mice lacking MafG exhibit mild neuronal phenotype and mild thrombocytopenia.[23] However, mice lacking Mafg and one allele of Mafk (Mafg-/-::Mafk+/-) exhibit progressive neuronal degeneration, thrombocytopenia and cataract,[26][27] and mice lacking MafG and MafK (Mafg-/-::Mafk-/-) exhibit more severe neuronal degeneration and die in the perinatal stage.[28] Mice lacking MafF, MafG and MafK are embryonic lethal.[29] Embryonic fibroblasts that are derived from Maff-/-::Mafg-/-::Mafk-/- mice fail to activate Nrf2-dependent cytoprotective genes in response to stress.[25]

Genotype Mouse Phenotype
Maff Mafg Mafk
−/− No apparent phenotype under laboratory conditions [23]
−/− Mild motor ataxia, mild thrombocytopenia [23]
−/− +/− Severe motor ataxia, progressive neuronal degeneration, severe thrombocytopenia, and cataract [26][27]
−/− −/− More severe neuronal phenotypes, and perinatal lethal [28]
−/− +/− −/− No severe abnormality [29] (Fertile)
−/− −/− −/− Growth retardation, fetal liver hypoplasia, and lethal around embryonic day, 13.5 [29]
+/− (heterozygote), −/− (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.

References

  1. 1 2 3 4 Fujiwara KT, Kataoka K, Nishizawa M (Sep 1993). "Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain". Oncogene 8 (9): 2371–80. PMID 8361754.
  2. 1 2 "Entrez Gene: MAFK v-maf musculoaponeurotic fibrosarcoma oncogene homolog K (avian)".
  3. 1 2 Andrews, NC (1993). "The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene.". Proc. Natl. Acad. Sci. USA. PMID 8265578.
  4. ↑ Petryszak R, Burdett T, Fiorelli B, Fonseca NA, Gonzalez-Porta M, Hastings E, Huber W, Jupp S, Keays M, Kryvych N, McMurry J, Marioni JC, Malone J, Megy K, Rustici G, Tang AY, Taubert J, Williams E, Mannion O, Parkinson HE, Brazma A (Jan 2014). "Expression Atlas update--a database of gene and transcript expression from microarray- and sequencing-based functional genomics experiments". Nucleic Acids Research 42 (Database issue): D926–32. doi:10.1093/nar/gkt1270. PMID 24304889.
  5. ↑ Katsuoka F, Motohashi H, Onodera K, Suwabe N, Engel JD, Yamamoto M (Jun 2000). "One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells". The EMBO Journal 19 (12): 2980–91. doi:10.1093/emboj/19.12.2980. PMID 10856242.
  6. ↑ Okita Y, Kamoshida A, Suzuki H, Itoh K, Motohashi H, Igarashi K, Yamamoto M, Ogami T, Koinuma D, Kato M (Jul 2013). "Transforming growth factor-β induces transcription factors MafK and Bach1 to suppress expression of the heme oxygenase-1 gene". The Journal of Biological Chemistry 288 (28): 20658–67. doi:10.1074/jbc.M113.450478. PMID 23737527.
  7. ↑ Wang R, Zheng J, Zhang DS, Yang YH, Zhao ZF (2015). "Wnt1-induced MAFK expression promotes osteosarcoma cell proliferation". Genetics and Molecular Research 14 (3): 7315–25. doi:10.4238/2015.July.3.7. PMID 26214410.
  8. ↑ Töröcsik B, Angelastro JM, Greene LA (Oct 2002). "The basic region and leucine zipper transcription factor MafK is a new nerve growth factor-responsive immediate early gene that regulates neurite outgrowth". The Journal of Neuroscience 22 (20): 8971–80. PMID 12388604.
  9. ↑ Ro YT, Jang BK, Shin CY, Park EU, Kim CG, Yang SI (2010). "Akt regulates the expression of MafK, synaptotagmin I, and syntenin-1, which play roles in neuronal function". Journal of Biomedical Science 17: 18. doi:10.1186/1423-0127-17-18. PMID 20233453.
  10. 1 2 3 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. doi:10.1038/367568a0. PMID 8107826.
  11. ↑ Johnsen O, Murphy P, Prydz H, Kolsto AB (Jan 1998). "Interaction of the CNC-bZIP factor TCF11/LCR-F1/Nrf1 with MafG: binding-site selection and regulation of transcription". Nucleic Acids Research 26 (2): 512–20. PMID 9421508.
  12. 1 2 Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y (Jul 1997). "An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements". Biochemical and Biophysical Research Communications 236 (2): 313–22. PMID 9240432.
  13. ↑ Kobayashi A, Ito E, Toki T, Kogame K, Takahashi S, Igarashi K, Hayashi N, Yamamoto M (Mar 1999). "Molecular cloning and functional characterization of a new Cap'n' collar family transcription factor Nrf3". The Journal of Biological Chemistry 274 (10): 6443–52. PMID 10037736.
  14. 1 2 Oyake T, Itoh K, Motohashi H, Hayashi N, Hoshino H, Nishizawa M, Yamamoto M, Igarashi K (Nov 1996). "Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site". Molecular and Cellular Biology 16 (11): 6083–95. PMID 8887638.
  15. ↑ Kataoka K, Igarashi K, Itoh K, Fujiwara KT, Noda M, Yamamoto M, Nishizawa M (Apr 1995). "Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor". Molecular and Cellular Biology 15 (4): 2180–90. PMID 7891713.
  16. ↑ Kurokawa H, Motohashi H, Sueno S, Kimura M, Takagawa H, Kanno Y, Yamamoto M, Tanaka T (Dec 2009). "Structural basis of alternative DNA recognition by Maf transcription factors". Molecular and Cellular Biology 29 (23): 6232–44. doi:10.1128/MCB.00708-09. PMID 19797082.
  17. 1 2 Otsuki A, Suzuki M, Katsuoka F, Tsuchida K, Suda H, Morita M, Shimizu R, Yamamoto M (Feb 2016). "Unique cistrome defined as CsMBE is strictly required for Nrf2-sMaf heterodimer function in cytoprotection". Free Radical Biology & Medicine 91: 45–57. doi:10.1016/j.freeradbiomed.2015.12.005. PMID 26677805.
  18. ↑ Friling RS, Bensimon A, Tichauer Y, Daniel V (Aug 1990). "Xenobiotic-inducible expression of murine glutathione S-transferase Ya subunit gene is controlled by an electrophile-responsive element". Proceedings of the National Academy of Sciences of the United States of America 87 (16): 6258–62. PMID 2166952.
  19. ↑ Rushmore TH, Morton MR, Pickett CB (Jun 1991). "The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity". The Journal of Biological Chemistry 266 (18): 11632–9. PMID 1646813.
  20. ↑ Mignotte V, Eleouet JF, Raich N, Romeo PH (Sep 1989). "Cis- and trans-acting elements involved in the regulation of the erythroid promoter of the human porphobilinogen deaminase gene". Proceedings of the National Academy of Sciences of the United States of America 86 (17): 6548–52. PMID 2771941.
  21. ↑ Romeo PH, Prandini MH, Joulin V, Mignotte V, Prenant M, Vainchenker W, Marguerie G, Uzan G (Mar 1990). "Megakaryocytic and erythrocytic lineages share specific transcription factors". Nature 344 (6265): 447–9. doi:10.1038/344447a0. PMID 2320113.
  22. ↑ Newman JR, Keating AE (Jun 2003). "Comprehensive identification of human bZIP interactions with coiled-coil arrays". Science 300 (5628): 2097–101. doi:10.1126/science.1084648. PMID 12805554.
  23. 1 2 3 4 5 Shavit JA, Motohashi H, Onodera K, Akasaka J, Yamamoto M, Engel JD (Jul 1998). "Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice". Genes & Development 12 (14): 2164–74. PMID 9679061.
  24. ↑ Shivdasani RA, Rosenblatt MF, Zucker-Franklin D, Jackson CW, Hunt P, Saris CJ, Orkin SH (Jun 1995). "Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development". Cell 81 (5): 695–704. PMID 7774011.
  25. 1 2 Katsuoka F, Motohashi H, Ishii T, Aburatani H, Engel JD, Yamamoto M (Sep 2005). "Genetic evidence that small maf proteins are essential for the activation of antioxidant response element-dependent genes". Molecular and Cellular Biology 25 (18): 8044–51. doi:10.1128/MCB.25.18.8044-8051.2005. PMID 16135796.
  26. 1 2 Katsuoka F, Motohashi H, Tamagawa Y, Kure S, Igarashi K, Engel JD, Yamamoto M (Feb 2003). "Small Maf compound mutants display central nervous system neuronal degeneration, aberrant transcription, and Bach protein mislocalization coincident with myoclonus and abnormal startle response". Molecular and Cellular Biology 23 (4): 1163–74. PMID 12556477.
  27. 1 2 Agrawal SA, Anand D, Siddam AD, Kakrana A, Dash S, Scheiblin DA, Dang CA, Terrell AM, Waters SM, Singh A, Motohashi H, Yamamoto M, Lachke SA (Jul 2015). "Compound mouse mutants of bZIP transcription factors Mafg and Mafk reveal a regulatory network of non-crystallin genes associated with cataract". Human Genetics 134 (7): 717–35. doi:10.1007/s00439-015-1554-5. PMID 25896808.
  28. 1 2 Onodera K, Shavit JA, Motohashi H, Yamamoto M, Engel JD (Mar 2000). "Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice". The EMBO Journal 19 (6): 1335–45. doi:10.1093/emboj/19.6.1335. PMID 10716933.
  29. 1 2 3 Yamazaki H, Katsuoka F, Motohashi H, Engel JD, Yamamoto M (Feb 2012). "Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf proteins". Molecular and Cellular Biology 32 (4): 808–16. doi:10.1128/MCB.06543-11. PMID 22158967.

Further reading

External links

This article is issued from Wikipedia - version of the Thursday, March 31, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.