CBFB

Core-binding factor subunit beta (CBFB) is a protein that in humans is encoded by the CBFB gene. It is a crucial component of the core-binding factor (CBF), a transcription factor that plays a significant role in the regulation of gene expression in hematopoietic (blood-forming) cells. The CBFB protein does not bind DNA directly; instead, it interacts with another subunit, RUNX1 (also known as AML1), enhancing its DNA-binding affinity and specificity. This interaction is vital for the proper regulation of genes involved in cell differentiation, cell cycle progression, and apoptosis (programmed cell death), particularly within the hematopoietic system.

Function

CBFB is an essential part of the core-binding factor complex, which is a heterodimeric transcription factor complex that includes RUNX1. This complex plays a critical role in the development and differentiation of various cell types, especially within the hematopoietic system. By binding to specific DNA sequences, the CBF complex regulates the expression of genes involved in cell proliferation, differentiation, and survival. The disruption of CBFB function has been implicated in the development of certain leukemias, highlighting its importance in maintaining normal blood cell development and function.

Clinical Significance

Mutations and chromosomal translocations involving the CBFB gene are associated with several forms of leukemia, most notably acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The most common translocation, t(8;21)(q22;q22), involves the CBFB gene and the RUNX1 gene. This translocation creates a fusion protein that acts as an aberrant transcription factor, disrupting normal cell differentiation and proliferation, leading to the development of leukemia.

Genetics

The CBFB gene is located on the short (p) arm of chromosome 16 at position 22. The gene encodes a protein that forms a complex with the RUNX1 protein, and this complex is a critical regulator of gene expression in hematopoietic cells. Mutations that affect the function or expression of CBFB can disrupt the regulation of gene expression, contributing to the development of leukemia.

Research

Research into CBFB has focused on understanding its role in normal hematopoiesis and how its disruption leads to leukemia. Studies have also explored potential therapeutic strategies targeting the aberrant CBFB-RUNX1 complex in leukemia cells. These strategies include the development of small molecules that can disrupt the interaction between CBFB and RUNX1, potentially restoring normal cell differentiation and proliferation.