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Acta Diabetologica

Erschienen in:

26.03.2016 | Original Article

Phosphorylation of MafA enhances interaction with Beta2/NeuroD1

verfasst von: Song-iee Han, Yukino Tsunekage, Kohsuke Kataoka

Erschienen in: Acta Diabetologica | Ausgabe 4/2016

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Abstract

Aims

MafA is a critical regulator of insulin expression and mature β-cell function. MafA binds to the insulin promoter through its carboxyl-terminal basic domain-leucine zipper (bZip) region and activates transcription synergistically with the β-cell-enriched transactivators Beta2 (NeuroD1) and Pdx1. MafA protein is highly phosphorylated in β-cells, and phosphorylation at multiple sites within its amino-terminal region is critical for its DNA-binding and transactivating abilities, as well as for regulation of its degradation. Here, we investigated whether phosphorylation of MafA affects its interaction with Beta2.

Methods

By mutational analysis, we identified interaction domains of MafA and Beta2. Using in situ proximity ligation assay (PLA), we explored mechanism of phosphorylation-dependent binding of MafA with Beta2. We also searched for a pathophysiological condition that would induce lower levels of MafA phosphorylation.

Results

Mutational analysis revealed that the phosphorylation sites within the amino-terminal region of MafA were not necessary for interaction with Beta2. In situ PLA suggested that phosphorylation induces conformational or configurational changes in MafA, thereby regulating the interaction with Beta2. We also found that long-term culture of the MIN6 insulinoma cell line under high-glucose conditions resulted in a decrease in β-cell-specific transcripts including insulin, along with a decrease in MafA phosphorylation and DNA binding.

Conclusion

Phosphorylation of MafA plays a critical role in β-cell function by regulating multiple functionalities, including binding to DNA, interaction with Beta2, and transactivation.

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Titel: Phosphorylation of MafA enhances interaction with Beta2/NeuroD1
verfasst von: Song-iee Han
Yukino Tsunekage
Kohsuke Kataoka
Publikationsdatum: 26.03.2016
Verlag: Springer Milan
Erschienen in: Acta Diabetologica / Ausgabe 4/2016
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-016-0853-1

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