Transcription factor MafB (MAFB) (MAFB)

Transcription factor MafB (MAFB) is a basic leucine zipper (bZIP) protein that serves as a master regulator of terminal differentiation in various tissues, most notably in the monocyte-macrophage lineage, pancreatic beta cells, and renal podocytes (UniProt Q9Y5Q3). It is a member of the large MAF family and acts as both a transcriptional activator and repressor to maintain cellular homeostasis and lineage commitment (PubMed: 27181683). In clinical oncology, MAFB is recognized as a potent oncogene, particularly in multiple myeloma, where chromosomal translocations such as t(14;20) lead to its aberrant overexpression, promoting tumor cell survival and resistance to proteasome inhibitors (PubMed: 15143098). Beyond cancer, mutations in MAFB are linked to rare genetic disorders like multicentric carpotarsal osteolysis (MCTO) and Duane retraction syndrome (PubMed: 28115588). Therapeutic interest in MAFB mRNA focuses on using RNA interference (siRNA) or antisense oligonucleotides (ASOs) to downregulate its expression in malignant cells or to modulate pathogenic macrophage responses in inflammatory diseases like COVID-19 (PubMed: 33208486). However, the target's essential role in normal physiological processes, such as insulin secretion and immune regulation, presents significant challenges for achieving therapeutic selectivity and safety (PubMed: 19892985).

Other names

V-maf musculoaponeurotic fibrosarcoma oncogene homolog BKRMLKreisler maf-related leucine zipper homologMaf-B

RNA interference-mediated mRNA degradation; antisense-mediated mRNA degradation; indirect modulation of protein stability via proteasome inhibition