Role of the DIP Molecules in DCC Signaling
Final rept. 1 Sep 1998-28 Feb 2001
WAYNE STATE UNIV DETROIT MI
Pagination or Media Count:
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 previous 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 apoptotic signal of DCC is mediated by the DIPs. During this funding period, we have identified a novel molecule named DIP13, cloned its full length cDNA sequence, determined its exon-intron structure, mapped its interacting domain with DCC, demonstrated that DIP13 expression induces apoptosis and obtained evidence showing that DIP13 interacts with AKT, a key molecule for cell survival. Our results suggest that the DCC apoptotic signal is mediated by DIP13 that interferes with AKT cell survival pathway, resulting in cell death. Finally, we have cloned DIP13 beta, suggesting that DIP13 represents a family of molecules with at least two members.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research