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]
Aramata S, Han SI, Yasuda K, Kataoka K (2005). "Synergistic activation of the insulin gene promoter by the beta-cell enriched transcription factors MafA, Beta2, and Pdx1". Biochim. Biophys. Acta. 1730 (1): 41–6.
doi:
10.1016/j.bbaexp.2005.05.009.
PMID15993959.
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]
Aramata S, Han SI, Yasuda K, Kataoka K (2005). "Synergistic activation of the insulin gene promoter by the beta-cell enriched transcription factors MafA, Beta2, and Pdx1". Biochim. Biophys. Acta. 1730 (1): 41–6.
doi:
10.1016/j.bbaexp.2005.05.009.
PMID15993959.