cMyb

c-Myb is a transcription factor belonging to the MYB family, encoded by the MYB gene in humans. The protein is defined by an N-terminal DNA-binding domain composed of three imperfect repeats (R1, R2, R3), known as the Myb DNA-binding domain, and a C-terminal regulatory region that contains activation and repression motifs.

Functionally, c-Myb regulates gene expression programs that control proliferation, differentiation, and survival of hematopoietic progenitor cells. It is essential for definitive hematopoiesis during development and contributes to the maintenance of hematopoietic stem and progenitor cell pools in the bone marrow. Its activity promotes progenitor cell expansion and influences lineage commitment, particularly toward myeloid and erythroid lineages, while downregulation is associated with differentiation.

Mechanistically, c-Myb binds to specific DNA sequences via its Myb domain and recruits transcriptional coactivators and components of the transcriptional machinery. It interacts with other transcription factors and regulatory proteins to modulate target genes involved in cell cycle progression and differentiation.

Clinical significance of c-Myb centers on its role as a proto-oncogene. Deregulation of MYB expression or disruptions in its regulatory networks are associated with hematologic malignancies, including various leukemias and lymphoid disorders. In research and clinical contexts, c-Myb activity is explored as a potential therapeutic target and as a biomarker of progenitor cell status.

Regulation and evolution: The MYB gene is conserved across vertebrates and is subject to tight developmental and signaling regulation. Protein levels are controlled at transcriptional, post-transcriptional, and post-translational levels.