The V-maf musculoaponeurotic fibrosarcoma oncogene K, commonly referred to as MafK, is a member of the Maf family of transcription factors. These proteins play a crucial role in regulating gene expression and are involved in various biological processes, including cell differentiation, proliferation, and apoptosis. The human recombinant form of MafK is a synthetically produced version of this protein, which is used in research and therapeutic applications.
The Maf family of transcription factors was first identified through the study of viral oncogenes. The v-Maf oncogene, which can cause musculoaponeurotic fibrosarcoma in vivo, was originally found in the genome of the avian transforming retrovirus AS42 . This discovery led to the identification of its cellular counterpart, c-Maf, and related genes, which comprise the Maf family. Maf proteins are classified into two subgroups based on their molecular size: large Mafs (approximately 240–340 amino acids) and small Mafs (approximately 150–160 amino acids) . MafK belongs to the small Maf subgroup.
MafK, like other Maf proteins, contains a basic leucine zipper (bZIP) domain, which allows it to bind DNA and regulate gene expression. The bZIP domain is composed of a basic region that binds to specific DNA sequences and a leucine zipper region that facilitates dimerization with other bZIP-containing proteins . MafK can form homodimers or heterodimers with other Maf proteins or members of the activator protein-1 (AP-1) superfamily, thereby modulating the expression of a wide range of genes.
MafK is involved in various cellular processes, including the regulation of the cell cycle, oxidative stress response, and inflammation . It plays a critical role in the differentiation of specific cell types, such as erythroid cells and pancreatic β-cells. In the context of pancreatic β-cell differentiation, MafK, along with other transcription factors like pancreatic duodenal homeobox 1 (PDX1) and neurogenin3 (NGN3), is essential for the reprogramming of human pancreatic duct-derived cells into insulin-secreting cells .
Dysregulation of MafK and other Maf proteins has been implicated in the development and progression of various cancers . MafK can influence tumorigenesis by modulating the expression of genes involved in cell proliferation, apoptosis, and metastasis. For instance, overexpression of MafK has been observed in certain types of leukemia and solid tumors, where it contributes to the malignant phenotype by promoting cell survival and proliferation .
The human recombinant form of MafK is used in research to study its role in cellular processes and disease. Additionally, it has potential therapeutic applications, particularly in the field of regenerative medicine. For example, synthetic modified mRNAs encoding MafK and other pancreatic transcription factors have been used to reprogram human pancreatic duct-derived cells into insulin-secreting cells, offering a promising approach for β-cell replacement therapy in patients with type 1 diabetes .