Mediation of the DCC Apoptotic Signal by DIP13α*

DCC (deleted in colorectal cancer) is a candidate tumor suppressor gene. However the function ofDCC remains elusive. Previously, we demonstrated that forced expression of DCC induces apoptosis or cell cycle arrest (Chen, Y. Q., Hsieh, J. T., Yao, F., Fang, B., Pong, R. C., Cipriano, S. C. & Krepulat, F. (1999) Oncogene 18, 2747–2754). To delineate the DCC-induced apoptotic pathway, we have identified a protein, DIP13α, which interacts with DCC. The DIP13α protein has a pleckstrin homology domain and a phosphotyrosine binding domain. It interacts with a region on the DCC cytoplasmic domain that is required for the induction of apoptosis. Although ectopic expression of DIP13α alone causes only a slight increase in apoptosis, co-expression of DCC and DIP13αresults in an ∼5-fold increase in apoptosis. Removal of the DCC-interacting domain on DIP13α abolishes its ability to enhance DCC-induced apoptosis. Inhibition of endogenous DIP13αexpression by small interfering RNA blocks DCC-induced apoptosis. Our data suggest that DIP13α is a mediator of the DCC apoptotic pathway.

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