TOX3
Description
The TOX3 (TOX high mobility group box family member 3) is a protein-coding gene located on chromosome 16.
TOX3 is a human gene encoding a transcription factor belonging to a subfamily that includes TOX, TOX2, and TOX4. These proteins share nearly identical HMG-box DNA-binding domains, which are responsible for altering chromatin structure by unwinding and bending DNA. TOX3 contains a glutamine-rich C-terminus due to CAG repeats. Located on chromosome band 16q12.1, TOX3 consists of seven exons and is highly expressed in the brain and luminal epithelial breast tissue. Mutations in TOX3 are linked to an increased susceptibility to breast cancer. This gene plays a role in regulating calcium-dependent transcription and interacts with CREB and CBP. It also enhances transcription through its interaction with CITED1, a transcription co-regulator that increases transcription factor activity. Mutations in TOX3, including the SNP rs3803662, have been associated with an elevated risk of breast cancer. This SNP is linked to reduced expression of TOX3 and a higher risk of breast cancer. The risk locus is believed to regulate the affinity of FOXA1 binding to chromatin, potentially influencing TOX3 expression.
TOX3 acts as a transcriptional coactivator within the p300/CBP-mediated transcription complex. It activates gene expression through cAMP response elements (CREs) and safeguards against cell death by promoting anti-apoptotic genes and suppressing pro-apoptotic genes. TOX3 stimulates transcription from estrogen-responsive and BCL-2 promoters. It is crucial for depolarization-induced activation of the C-FOS promoter in neurons and associates with chromatin at the estrogen-responsive C3 promoter region.
TOX3 is also known as CAGF9, TNRC9.
