MAF

Maf refers to a family of transcription factors known as Maf proteins. The name originates from the oncogene musculoaponeurotic fibrosarcoma. Maf proteins are basic leucine zipper (bZIP) transcription factors that bind DNA as dimers at Maf recognition elements (MAREs) to regulate gene expression. The family is divided into two main subfamilies: large Mafs, which include c-Maf, MafA, and MafB, and small Mafs, which include MafF, MafG, and MafK. Large Mafs contain transactivation domains and can activate transcription on their own, while small Mafs lack these domains and typically function as transcriptional partners, forming heterodimers with other bZIP proteins such as Nrf2 or Fos/Jun.

Functions of Maf proteins are diverse and essential for development and cellular differentiation across tissues. MafA is important for mature pancreatic beta cells, where it regulates insulin gene expression and glucose-stimulated insulin secretion. MafB participates in pancreatic development and macrophage differentiation. c-Maf has roles in lens development and in T helper cell differentiation, among other processes. Small Mafs modulate activity by partnering with other transcription factors to regulate stress responses, metabolism, and other pathways.

Clinical relevance is evident in cancer biology. Aberrant expression or chromosomal rearrangements involving MAF genes are linked to certain cancers, notably multiple myeloma, where translocations can lead to overexpression of Maf proteins such as c-Maf or MAFB, contributing to disease progression.

Evolution and regulation: Maf proteins are conserved across vertebrates and function within broader transcriptional networks, often cooperating with other factors to fine-tune gene expression. Regulation occurs at transcriptional and post-translational levels, including phosphorylation and ubiquitination, influencing their stability and activity.