Role of the DIP Molecules in DCC Signaling
Annual rept. 1 Sep 1998-31 Aug 1999
WAYNE STATE UNIV DETROIT MI
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Inactivation of tumor suppressor genes plays a causal role in the development of human cancers. The Deleted in Colorectal Cancer DCC gene is a putative tumor suppressor gene. Loss of heterozygosity at the DCC locus and loss of DCC expression has been observed in prostate cancer. Our recent data indicate that DCC expression induces apoptosis and cell cycle arrest of prostate tumor cells. By yeast two-hybrid screening, we have identified molecules that interact with the DCC cytoplasmic domain dubbed DCC interacting proteins or DIPs. We hypothesize that the cytoplasmic domain of DCC transduces a signal resulting in either activation of caspase which induces apoptosis or inhibition of Cdk1 kinase activity which leads to G2M cycle arrest, and this signal of DCC is mediated by the DIPs. To understand the mechanism by which DCC induces apoptosis and cycle arrest, we propose to study the role of DIPs in DCC signaling. In the last 12 months, we have partially completed our task1. Moreover, we performed extra experiments by cloning two novel genes. The major accomplishments are 1 Truncation of the DCC cytoplasmic domain 2 Tagging of DCC and hsina, FKBP12 3 Cloning of two novel genes, Dip5 and Dip13, and 4 Tagging Dip5 and Dip13.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology