RUNX3
Description
The RUNX3 (RUNX family transcription factor 3) is a protein-coding gene located on chromosome 1.
RUNX3 is a protein that plays a crucial role in gene regulation. It belongs to a family of transcription factors containing a 'runt domain,' which allows them to bind to specific DNA sequences and control gene activity. RUNX3 forms a complex with another protein called CBFB, creating the core-binding factor (CBF). This complex binds to specific DNA sequences in the regulatory regions of genes, influencing their activity. RUNX3 is known to act as a tumor suppressor, meaning it helps to prevent cancer development. It is often found to be deleted or silenced in cancer cells, highlighting its importance in controlling cell growth and differentiation. Multiple versions of the RUNX3 gene exist, each producing a slightly different version of the protein. In melanocytic cells (skin pigment cells), RUNX3 expression is regulated by another protein called MITF. RUNX3 actively participates in protecting against the early stages of tumor formation. It can be modified by another protein (p300) in response to growth factors, leading to the formation of a complex with another protein called BRD2. This complex then promotes the production of two important proteins: CDKN1A and ARF. CDKN1A helps to control cell growth by halting the cell cycle, while ARF prevents the breakdown of p53, a protein known for its tumor-suppressing activity. The activity of CDKN1A and ARF is temporary due to the replacement of the RUNX3-BRD2 complex by another complex involving cyclinD1. However, if certain signals associated with cancer development are present (like KRASG12D), the RUNX3-BRD2 complex remains active, leading to the constant production of p21, ARF, and p53, further suppressing tumor growth.
RUNX3 forms a complex called core-binding factor (CBF) by partnering with CBFB. This complex controls gene activity by recognizing specific DNA sequences (5'-TGTGGT-3' or rarely 5'-TGCGGT-3') within gene regulatory regions. RUNX3's 'runt domain' is responsible for this DNA binding. CBFB, while not directly binding DNA, enhances RUNX3's DNA binding ability. CBF complexes regulate a variety of genes, including those involved in viral activity (murine leukemia virus, polyomavirus), immune cell development (T-cell receptor enhancers, LCK), and growth factors (IL3, GM-CSF). RUNX3 might play a role in controlling cell growth and differentiation. In collaboration with ZFHX3, RUNX3 boosts the activity of the CDKN1A gene following TGF-beta signaling. CBF complexes are also involved in the development of cytotoxic T cells, suppressing the activity of the ZBTB7B gene. This suppression involves binding to a specific region in the ZBTB7B gene and recruiting other proteins that modify the surrounding DNA, leading to long-term silencing of ZBTB7B.
RUNX3 is also known as AML2, CBFA3, PEBP2aC.
