From Wikipedia, the free encyclopedia
MAFA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases MAFA, RIPE3b1, hMafA, MAF bZIP transcription factor A, INSDM
External IDs OMIM: 610303; MGI: 2673307; HomoloGene: 65867; GeneCards: MAFA; OMA: MAFA - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_201589

NM_194350

RefSeq (protein)

NP_963883

NP_919331

Location (UCSC) Chr 8: 143.42 – 143.43 Mb Chr 15: 75.62 – 75.62 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transcription factor MafA is a protein that in humans is encoded by the MAFA gene. [5] It is a member of the Maf family of transcription factors. [6]

MAFA is phosphorylated sequentially on four serine/threonine residues by GSK-3 kinase. [7] These phosphorylations activate MAFA transcription and trigger its degradation in the proteasome. Altering these post-translationnal modifications leads to severe pathological consequences. Mutation of these  residues  is perinatally lethal in mice, [8] and  mutation of the Ser64Phe priming site was reported to induce familial diabetes mellitus and insulinomatosis in humans. [9]

MAFA assists in insulin regulation

An in vivo study on mice proved MafA binds to the promoter in an insulin gene to regulate insulin transcription in response to serum glucose levels. [10] MafA is a β cell-specific activator, which differentiates it from other transcription factors involved with insulin gene expression. [11] It helps regulate the β cells involved with insulin secretion primarily by maintaining β cell metabolism. [12] The amount of MafA in the β cells is regulated by levels of glucose and oxidative stress. [6]

Interactions

MafA (gene) has been shown to interact with NEUROD1 [13] and Pdx1. [13] MafA works with Pdx1 to activate the insulin gene. [6]

MAFA in neurons

In addition to its expression in pancreatic ßcells, MAFA is also expressed in specific subsets of  excitatory and inhibitory neurons. In the peripheric nervous system, it is expressed in touch mechanoreceptors. [14] [15]  In the central nervous system,  Mafa is expressed in sensory neurons in the spinal cord and trigeminal nucleus, as well as in the olfactory bulb. It is also present in ventral inhibitory neurons of the spinal cord (Renshaw cells) and in brainstem inhibitory neurons controlling  mouse neonatal apneas. [8]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000182759Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000047591Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: MAFA v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (avian)".
  6. ^ a b c Aramata; Han (2007). "Roles and Regulation of Transcription Factor MafA in Islet β-cells". Endocr. J. 54 (5): 659–66. doi: 10.1507/endocrj.kr-101. PMID  17785922.
  7. ^ Rocques, Nathalie; Abou Zeid, Nancy; Sii-Felice, Karine; Lecoin, Laure; Felder-Schmittbuhl, Marie-Paule; Eychène, Alain; Pouponnot, Celio (November 2007). "GSK-3-Mediated Phosphorylation Enhances Maf-Transforming Activity". Molecular Cell. 28 (4): 584–597. doi: 10.1016/j.molcel.2007.11.009. PMID  18042454.
  8. ^ a b Lecoin, Laure; Dempsey, Bowen; Garancher, Alexandra; Bourane, Steeve; Ruffault, Pierre-Louis; Morin-Surun, Marie-Pierre; Rocques, Nathalie; Goulding, Martyn; Eychène, Alain; Pouponnot, Celio; Fortin, Gilles; Champagnat, Jean (June 2022). "Mafa-dependent GABAergic activity promotes mouse neonatal apneas". Nature Communications. 13 (1): 3284. Bibcode: 2022NatCo..13.3284L. doi: 10.1038/s41467-022-30825-3. ISSN  2041-1723. PMC  9174494. PMID  35672398.
  9. ^ Iacovazzo, Donato; Flanagan, Sarah E.; Walker, Emily; Quezado, Rosana; de Sousa Barros, Fernando Antonio; Caswell, Richard; Johnson, Matthew B.; Wakeling, Matthew; Brändle, Michael; Guo, Min; Dang, Mary N.; Gabrovska, Plamena; Niederle, Bruno; Christ, Emanuel; Jenni, Stefan (30 January 2018). "MAFA missense mutation causes familial insulinomatosis and diabetes mellitus". Proceedings of the National Academy of Sciences. 115 (5): 1027–1032. Bibcode: 2018PNAS..115.1027I. doi: 10.1073/pnas.1712262115. ISSN  0027-8424. PMC  5798333. PMID  29339498.
  10. ^ Zhang; Moriguchi (2005). "MafA Is a Key Regulator of Glucose-Stimulated Insulin Secretion". Mol. Cell. Biol. 25 (12): 4969–4976. doi: 10.1128/MCB.25.12.4969-4976.2005. PMC  1140590. PMID  15923615.
  11. ^ Matsuoka; Artner (March 2004). "The MafA transcription factor appears to be responsible for tissue-specific expression of insulin". Proc. Natl. Acad. Sci. U.S.A. 101 (9): 2930–3. Bibcode: 2004PNAS..101.2930M. doi: 10.1073/pnas.0306233101. PMC  365722. PMID  14973194.
  12. ^ Wang; Kataoka (2007). "MAFA controls genes implicated in insulin biosynthesis and secretion". Diabetologia. 50 (2): 348–58. doi: 10.1007/s00125-006-0490-2. PMC  2196442. PMID  17149590.
  13. ^ a b Zhao, Li; Guo Min; Matsuoka Taka-Aki; Hagman Derek K; Parazzoli Susan D; Poitout Vincent; Stein Roland (March 2005). "The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription". J. Biol. Chem. 280 (12): 11887–94. doi: 10.1074/jbc.M409475200. ISSN  0021-9258. PMID  15665000.
  14. ^ Bourane, Steeve; Garces, Alain; Venteo, Stephanie; Pattyn, Alexandre; Hubert, Thomas; Fichard, Agnes; Puech, Sylvie; Boukhaddaoui, Hassan; Baudet, Christel; Takahashi, Satoru; Valmier, Jean; Carroll, Patrick (December 2009). "Low-Threshold Mechanoreceptor Subtypes Selectively Express MafA and Are Specified by Ret Signaling". Neuron. 64 (6): 857–870. doi: 10.1016/j.neuron.2009.12.004. PMID  20064392. S2CID  14370290.
  15. ^ Lecoin, Laure; Rocques, Nathalie; El-Yakoubi, Warif; Achour, Sarrah Ben; Larcher, Magalie; Pouponnot, Celio; Eychène, Alain (2010). "MafA transcription factor identifies the early ret-expressing sensory neurons". Developmental Neurobiology. 70 (7): 485–497. doi: 10.1002/dneu.20790. PMID  20213756. S2CID  421285.

Further reading


From Wikipedia, the free encyclopedia
MAFA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases MAFA, RIPE3b1, hMafA, MAF bZIP transcription factor A, INSDM
External IDs OMIM: 610303; MGI: 2673307; HomoloGene: 65867; GeneCards: MAFA; OMA: MAFA - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_201589

NM_194350

RefSeq (protein)

NP_963883

NP_919331

Location (UCSC) Chr 8: 143.42 – 143.43 Mb Chr 15: 75.62 – 75.62 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transcription factor MafA is a protein that in humans is encoded by the MAFA gene. [5] It is a member of the Maf family of transcription factors. [6]

MAFA is phosphorylated sequentially on four serine/threonine residues by GSK-3 kinase. [7] These phosphorylations activate MAFA transcription and trigger its degradation in the proteasome. Altering these post-translationnal modifications leads to severe pathological consequences. Mutation of these  residues  is perinatally lethal in mice, [8] and  mutation of the Ser64Phe priming site was reported to induce familial diabetes mellitus and insulinomatosis in humans. [9]

MAFA assists in insulin regulation

An in vivo study on mice proved MafA binds to the promoter in an insulin gene to regulate insulin transcription in response to serum glucose levels. [10] MafA is a β cell-specific activator, which differentiates it from other transcription factors involved with insulin gene expression. [11] It helps regulate the β cells involved with insulin secretion primarily by maintaining β cell metabolism. [12] The amount of MafA in the β cells is regulated by levels of glucose and oxidative stress. [6]

Interactions

MafA (gene) has been shown to interact with NEUROD1 [13] and Pdx1. [13] MafA works with Pdx1 to activate the insulin gene. [6]

MAFA in neurons

In addition to its expression in pancreatic ßcells, MAFA is also expressed in specific subsets of  excitatory and inhibitory neurons. In the peripheric nervous system, it is expressed in touch mechanoreceptors. [14] [15]  In the central nervous system,  Mafa is expressed in sensory neurons in the spinal cord and trigeminal nucleus, as well as in the olfactory bulb. It is also present in ventral inhibitory neurons of the spinal cord (Renshaw cells) and in brainstem inhibitory neurons controlling  mouse neonatal apneas. [8]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000182759Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000047591Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: MAFA v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (avian)".
  6. ^ a b c Aramata; Han (2007). "Roles and Regulation of Transcription Factor MafA in Islet β-cells". Endocr. J. 54 (5): 659–66. doi: 10.1507/endocrj.kr-101. PMID  17785922.
  7. ^ Rocques, Nathalie; Abou Zeid, Nancy; Sii-Felice, Karine; Lecoin, Laure; Felder-Schmittbuhl, Marie-Paule; Eychène, Alain; Pouponnot, Celio (November 2007). "GSK-3-Mediated Phosphorylation Enhances Maf-Transforming Activity". Molecular Cell. 28 (4): 584–597. doi: 10.1016/j.molcel.2007.11.009. PMID  18042454.
  8. ^ a b Lecoin, Laure; Dempsey, Bowen; Garancher, Alexandra; Bourane, Steeve; Ruffault, Pierre-Louis; Morin-Surun, Marie-Pierre; Rocques, Nathalie; Goulding, Martyn; Eychène, Alain; Pouponnot, Celio; Fortin, Gilles; Champagnat, Jean (June 2022). "Mafa-dependent GABAergic activity promotes mouse neonatal apneas". Nature Communications. 13 (1): 3284. Bibcode: 2022NatCo..13.3284L. doi: 10.1038/s41467-022-30825-3. ISSN  2041-1723. PMC  9174494. PMID  35672398.
  9. ^ Iacovazzo, Donato; Flanagan, Sarah E.; Walker, Emily; Quezado, Rosana; de Sousa Barros, Fernando Antonio; Caswell, Richard; Johnson, Matthew B.; Wakeling, Matthew; Brändle, Michael; Guo, Min; Dang, Mary N.; Gabrovska, Plamena; Niederle, Bruno; Christ, Emanuel; Jenni, Stefan (30 January 2018). "MAFA missense mutation causes familial insulinomatosis and diabetes mellitus". Proceedings of the National Academy of Sciences. 115 (5): 1027–1032. Bibcode: 2018PNAS..115.1027I. doi: 10.1073/pnas.1712262115. ISSN  0027-8424. PMC  5798333. PMID  29339498.
  10. ^ Zhang; Moriguchi (2005). "MafA Is a Key Regulator of Glucose-Stimulated Insulin Secretion". Mol. Cell. Biol. 25 (12): 4969–4976. doi: 10.1128/MCB.25.12.4969-4976.2005. PMC  1140590. PMID  15923615.
  11. ^ Matsuoka; Artner (March 2004). "The MafA transcription factor appears to be responsible for tissue-specific expression of insulin". Proc. Natl. Acad. Sci. U.S.A. 101 (9): 2930–3. Bibcode: 2004PNAS..101.2930M. doi: 10.1073/pnas.0306233101. PMC  365722. PMID  14973194.
  12. ^ Wang; Kataoka (2007). "MAFA controls genes implicated in insulin biosynthesis and secretion". Diabetologia. 50 (2): 348–58. doi: 10.1007/s00125-006-0490-2. PMC  2196442. PMID  17149590.
  13. ^ a b Zhao, Li; Guo Min; Matsuoka Taka-Aki; Hagman Derek K; Parazzoli Susan D; Poitout Vincent; Stein Roland (March 2005). "The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription". J. Biol. Chem. 280 (12): 11887–94. doi: 10.1074/jbc.M409475200. ISSN  0021-9258. PMID  15665000.
  14. ^ Bourane, Steeve; Garces, Alain; Venteo, Stephanie; Pattyn, Alexandre; Hubert, Thomas; Fichard, Agnes; Puech, Sylvie; Boukhaddaoui, Hassan; Baudet, Christel; Takahashi, Satoru; Valmier, Jean; Carroll, Patrick (December 2009). "Low-Threshold Mechanoreceptor Subtypes Selectively Express MafA and Are Specified by Ret Signaling". Neuron. 64 (6): 857–870. doi: 10.1016/j.neuron.2009.12.004. PMID  20064392. S2CID  14370290.
  15. ^ Lecoin, Laure; Rocques, Nathalie; El-Yakoubi, Warif; Achour, Sarrah Ben; Larcher, Magalie; Pouponnot, Celio; Eychène, Alain (2010). "MafA transcription factor identifies the early ret-expressing sensory neurons". Developmental Neurobiology. 70 (7): 485–497. doi: 10.1002/dneu.20790. PMID  20213756. S2CID  421285.

Further reading



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