MAFA

MAFA, or MafA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A), is a transcription factor belonging to the large Maf family. It contains a basic region leucine zipper (bZIP) DNA-binding domain and binds Maf recognition elements (MARE) in target gene promoters to regulate transcription.

In mammals, MAFA is predominantly expressed in pancreatic beta cells and is a key regulator of insulin gene transcription and beta-cell maturation. It works together with other beta-cell transcription factors such as PDX1 and NeuroD1 to promote glucose-stimulated insulin secretion. MAFA activity is developmentally regulated and considered essential for the mature, functional beta-cell phenotype in many species.

Developmental and species differences accompany MAFA function. In mice, MafA becomes the principal mature beta-cell Maf factor after birth, while MafB is expressed earlier and is gradually replaced. In humans, MafA remains important in adult beta cells, though species-specific expression patterns can differ.

MAFA activity is modulated by glucose levels and cellular signaling pathways; post-translational modifications, including phosphorylation, influence its stability and transcriptional activity. Oxidative stress and chronic hyperglycemia can reduce MAFA expression or function, contributing to beta-cell dysfunction in diabetes. Rare germline MAFA mutations have been linked to familial forms of diabetes and insulinomatosis, and some variants can alter transcriptional activity or stability, with clinical consequences.

Overall, MAFA is recognized as a central regulator of mature beta-cell identity and insulin secretory capacity, playing a critical role in maintaining glucose homeostasis.