CBFA2T - CBFA2/RUNX1 partner transcriptional co-repressor | Elisa - Clia - Antibody - Protein

Background

CBFA2T, also known as CBFA2/RUNX1 Partner Transcriptional Co-Repressor, is a crucial protein involved in the regulation of gene expression. It was originally identified as a fusion partner in the t(8;21) chromosomal translocation commonly found in acute myeloid leukemia (AML). This translocation results in the creation of the RUNX1-ETO (also known as AML1-ETO) fusion protein, which disrupts normal hematopoiesis and contributes to leukemogenesis. CBFA2T is part of a larger family of proteins known as the ETO (Eight Twenty-One) family, which are characterized by their roles in transcriptional repression and chromatin remodeling.

Protein Structure

CBFA2T proteins typically have several conserved domains that facilitate their function:

• NHR1 (Nervy Homology Region 1): This domain interacts with other transcriptional regulators.
• NHR2: Facilitates homo- and hetero-dimerization, essential for the formation of multi-protein complexes.
• NHR3 and NHR4: Involved in binding to other co-repressors and chromatin remodeling proteins.

The modular structure of CBFA2T allows it to interact with various partners and integrate multiple signaling pathways to modulate gene expression.

Classification and Subtypes

The CBFA2T family includes several members, with CBFA2T1, CBFA2T2, and CBFA2T3 being the most studied. Each member has unique and overlapping functions in different tissues and developmental stages:

• CBFA2T1 (ETO): The most well-known member, frequently involved in leukemogenesis.
• CBFA2T2: Plays roles in neurogenesis and other developmental processes.
• CBFA2T3: Involved in hematopoiesis and immune system regulation.

Function and Biological Significance

CBFA2T proteins are primarily involved in transcriptional repression. They function by recruiting histone deacetylases (HDACs) and other chromatin remodeling complexes to specific gene promoters, leading to a closed chromatin conformation and suppression of gene expression. This repression is crucial for regulating genes involved in cell differentiation, proliferation, and apoptosis.

Clinical Issues

• Acute Myeloid Leukemia (AML): The CBFA2T1/RUNX1 (AML1-ETO) fusion protein resulting from t(8;21) translocation is a hallmark of a subset of AML cases. This fusion protein acts as a dominant repressor of RUNX1 target genes, blocking normal myeloid differentiation and promoting leukemogenesis.
• Other Cancers: Dysregulation of CBFA2T family members has been implicated in various cancers, including solid tumors and lymphomas. The precise mechanisms often involve disruption of normal transcriptional repression and chromatin remodeling pathways.
• Developmental Disorders: Mutations and aberrant expression of CBFA2T family members are linked to developmental disorders, reflecting their roles in neurogenesis and hematopoiesis.

Summary

CBFA2T proteins, including CBFA2T1, CBFA2T2, and CBFA2T3, are vital transcriptional co-repressors involved in regulating gene expression through chromatin remodeling. Their roles in normal hematopoiesis and neurogenesis underscore their importance in development and disease. The t(8;21) translocation and resulting RUNX1-ETO fusion protein are particularly significant in the context of AML, illustrating the critical impact of CBFA2T dysregulation in leukemogenesis. Understanding the detailed mechanisms of CBFA2T function and its interactions with other cellular pathways continues to be an important area of research, with implications for targeted therapies in cancer and other diseases.