9319178 Etkin The function of many nuclear proteins is regulated by selective nuclear localization. Xenopus nuclear factor 7 (xnf7), a putative transcription factor, is a member of a novel zinc finger gene family whose members consist primarily of transcription factors and protooncogenes. Xnf7 is first detected in the oocyte nucleus and is retained in the cytoplasm until the mid blastula stage of development when it reenters the nucleus. Recent evidence showed that a 22 amino acid sequence in xnf7 called the cytoplasmic retention domain (CRD) is required for cytoplasmic retention prior to the mid blastula stage and that phosphorylation of two sites within the protein is necessary for proper CRD function. Dr. Etkin's laboratory has shown that xnf7 is retained in the cytoplasm through an anchor mechanism most likely involving the tethering to a ctyoplasmic anchor protein. The hypothesis being tested in this project is that phosphorylation induces a structural change in xnf7 resulting in the binding of the CRD sequence to an anchor protein. Dr. Etkin will test this hypothesis by accomplishing the following specific aims: (1) He will further determine the role of phosphorylation in the retention of xnf7 in the cytoplasm. (2) He will analyze and identify the proteins that interact with the CRD sequence and function in cytoplasmic retention of xnf7 and will clone the cDNAs for these proteins. In addition to gaining an insight into an important regulatory process during amphibian development, the analysis of the mechanism of selective nuclear localization of xnf7 will provide information necessary to understand this phenomenon in other systems. ***
