The current focus is on metablastin, a highly conserved cytosolic protein, discovered in this laboratory, that undergoes serine phosphorylation in response to a variety of extracellular factors, and during the cell cycle. It is expressed in most immature cells during mammalian development and in many cancer cells. To explore its biological function, we have deleted one allele of the metablastin gene in mouse embryonic stem cells using gene targeting, and introduced the deletion into the germ line of mice.
Studies are in progress to characterize the phenotype of the metablastin knockout mice.
To elucidate the biochemical function of metablastin, we have isolated a novel human cDNA that encodes metablastin-interacting protein, Mip1, using a yeast twohybrid interaction screen. Current studies are aimed at characterizing the structure, expression, and function of Mip1. Preliminary evidence suggests metablastin plays a role in cell cycle regulation. Our hypothesis is that Mip1 and metablastin are components of a cell cycle checkpoint that is controlled through phosphorylation of metablastin by the principal CDK of the cell cycle, p34cdc2. This work will provide new insights into the mechanism of cell cycle regulation.