The MAFB gene (MAF bZIP Transcription Factor B) is a gene found in humans and other organisms. The protein produced from this gene regulates various biological processes. Understanding MAFB helps explain normal cell development and function, and how disruptions can lead to health conditions.
MAFB’s Normal Functions
MAFB plays a role in the development and function of several cell types and organs. It is involved in hematopoiesis, the process by which blood cells form and mature. Specifically, MAFB helps regulate the differentiation of myeloid cells, a type of white blood cell, and is particularly expressed in macrophages. Macrophages are immune cells that help maintain the body’s balance and restrain the immune system.
MAFB also contributes to bone development and the formation of osteoclasts, which are cells responsible for breaking down bone tissue. This gene is active in renal development, influencing the morphology and function of podocytes, specialized cells in the kidney. Additionally, MAFB is involved in the differentiation of pancreatic alpha and beta cells, which are responsible for producing hormones like glucagon and insulin. Its presence has also been observed in epidermal keratinocytes, hair follicles, and hematopoietic stem cells.
How MAFB Regulates Cellular Processes
MAFB functions as a “transcription factor,” a type of protein that controls which genes are turned on or off within a cell. It belongs to the basic leucine zipper (bZIP) family of proteins, characterized by a specific structure that allows them to interact with DNA. MAFB binds to particular DNA sequences, known as Maf recognition elements (MAREs), in the promoter regions of other genes.
By binding to these specific DNA sites, MAFB can either activate or repress the expression of those target genes. This regulation influences various cellular activities, including cell development, differentiation, and overall function. MAFB’s ability to bind DNA and modulate gene activity is central to its roles in biological processes.
MAFB in Disease Development
Mutations or irregular MAFB activity are linked to specific human diseases. One such condition is Multicentric Carpotarsal Osteolysis Syndrome (MCTO), a rare genetic disorder characterized by the progressive destruction of the small bones in the wrists (carpals) and ankles (tarsals). Individuals with MCTO often experience joint pain, deformity, and limited movement, which can begin in early childhood. This syndrome can also lead to kidney problems, including proteinuria, and may progress to renal failure. Some cases also involve intellectual disability or facial abnormalities.
MAFB dysregulation is also implicated in certain cancers, demonstrating its dual nature as either an oncogene or a tumor suppressor depending on the cellular context. In multiple myeloma, a cancer of plasma cells, MAFB is frequently overexpressed due to chromosomal translocations. High levels of MAFB protein in multiple myeloma cells can contribute to resistance against certain cancer treatments, such as proteasome inhibitors, by preventing MAFB protein degradation. Altered MAFB activity has also been linked to the proliferation of hepatocellular carcinoma (liver cancer) cells.