M33 (gene)

M33, also known as Polycomb protein homolog M33 or BMI1, is a gene that encodes a protein involved in the Polycomb Repressive Complex 1 (PRC1). In mammals, the gene is often referred to as BMI1. PRC1 is a crucial epigenetic regulator involved in various cellular processes including stem cell maintenance, cell differentiation, cell proliferation, and tumorigenesis.

The M33/BMI1 protein functions as a component of PRC1, which plays a role in gene silencing through histone modification, particularly through ubiquitination of histone H2A at lysine 119 (H2AK119ub1). This modification is associated with transcriptional repression and is important for maintaining the silenced state of genes involved in development and differentiation.

Dysregulation of M33/BMI1 expression has been implicated in the development and progression of various cancers, including leukemia, lymphoma, and solid tumors. Overexpression of M33/BMI1 can promote tumorigenesis by silencing tumor suppressor genes and enhancing self-renewal capacity of cancer stem cells. Conversely, loss-of-function mutations or decreased expression can disrupt normal development and cell differentiation.

The specific effects of M33/BMI1 on cellular processes and cancer development are context-dependent and can vary depending on the cell type, the presence of other genetic and epigenetic alterations, and the specific signaling pathways involved. Research continues to elucidate the precise mechanisms by which M33/BMI1 contributes to both normal development and disease pathogenesis.

M33 is evolutionarily conserved, with homologs found in various organisms, including Drosophila, where it was originally identified as a component of the Polycomb group (PcG) proteins. These PcG proteins are essential for maintaining cell identity and regulating developmental gene expression throughout the lifespan of the organism.