Honorable Mention!
Determining the binding domain of the Z-DNA binding protein for the negative regulatory element of the ADAM-12 gene, Chang, Jordan
College of Science and Mathematics
ADAM-12 is a multifunctional protein that is involved in cell communication and cell growth. This gene appears to play a vital role in many cancers and tumor formations. While expression of ADAM-12 is generally low in adult human tissues, cancer cells are seen to have remarkably high levels of expression of this protein. In an attempt to regulate ADAM-12 expression, negative regulatory elements (NRE), located upstream of the ADAM-12 gene, are suspected to inhibit the translation of the ADAM-12 gene. This is done through the interaction of a Z-DNA binding protein. While the identity of the Z-DNA binding protein is unknown as well as how this interaction occurs, we hypothesize that the Z-DNA binding protein blocks DNA polymerase from initiating the translation of the ADAM-12 gene. We propose to identify the sequence and structure of the Z-DNA binding protein for the NRE of the ADAM-12 gene. This can be done by first isolating the protein through affinity chromatography from human cancer cells and then, using X-ray crystallography or NMR, determine the sequence and structure of the protein. To identify the Z-DNA binding domain of the protein, we propose to use the sequence we determine in a multiple sequence alignment with other known Z-DNA binding proteins. This will provide a better understanding of this inhibitory mechanism and possibly present new therapies to battle against cancer and tumor growth.
