IXL, a new subunit of the mammalian Mediator complex, functions as a transcriptional suppressor

Transcription factors play an essential role in altering gene expression. Much progress about transcription factors has been made toward the understanding of normal physiological processes, embryonic development, and human diseases. In the present study, we report the identification and characterization of a novel human gene, (Drosophila) intersex-like (IXL), from a human embryonic heart cDNA library. IXL encodes a putative protein of 221 amino acids. The protein is conserved across different species during evolution. Northern blot analysis indicates that IXL is expressed in various tissues of human adult and during three different developmental stages of embryo. In COS-7 cells, IXL protein is localized to nucleus and cytoplasm. IXL is a transcription suppressor when fused to Gal-4 DNA-binding domain and cotransfected with VP-16. Overexpression of IXL in COS-7 cells inhibits the transcriptional activities of SRE and AP-1, suggesting that the IXL protein may act as a transcriptional suppressor in mitogen-activated protein kinase signaling pathway to mediate cellular functions.