Mechanisms of transcriptional repression by the oncoprotein Qin

The oncogene qin was isolated from a chicken tumor in 1992. Intense expression (production) of the protein Qin, encoded by the qin gene, results in cell transformation, a term describing uncontrolled growth which may lead to cancer. In humans, a protein related to Qin is called brain factor 1. Both proteins belong to a newly defined family of transcription factors, the "winged helix (WH) proteins", which positively or negatively regulate the transcription of specific genes and therefore the production of the encoded proteins. Several other WH proteins are known to be causally involved in human cancer. Qin binds to a specific DAN-sequence and represses transcription of genes near this sequence. Little is known about the mechanisms of transcriptional repression. I will define the minimal part of Qin required for repression. I will analyse the binding of putative interaction partners (e.g. proteins of the transcription initiation and regulation machinery) to the repression domain of Qin in vitro. The genes of these proteins and qin will be cloned in chicken cells to observe effects of Qin-binding partners on Qin-induced transformation and repression. These experiments have the potential of revealing critical aspects of Qin-induced repression and transformation and of repression mechanisms in general. Most proteins involved in cellular transformation are parts of signal transduction cascades, which culminate in the regulation of gene expression through transcription factors, like Qin. The study of Qin may open new aspects to understanding and treating cancer.