Training Plan: The applicant proposes to study the signalling molecules involved in FasL signaling and apoptosis. Using the yeast two-hybrid system, Dr. Zakalik identified a cDNA encoding a protein (Flap-1) which interacts with the cytoplasmic domain of FasL and has high homology with a protein (mSin3B) and is similar to a yeast transcriptional repressor. The applicant will explore the role of Flap-1, its ability to form complexes with Mad/Max and Mad/Mxi1 leading to decreased transcription of myc-responsive genes. If FasL then regulates myc, which is involved with activation-induced apoptosis in T cells, then the applicant will examine the possibility that overexpression of Flap-1 will antagonize myc-dependent apoptosis.
