Three possible examples of tumor-specific targeting using E1A fusion proteins. In each case E1A is fused to a protein domain (X) that binds to a protein normally found at the promoter in increased amounts in tumor cells. Notch Pathway: in the absence of a signal, CSL recruits co-repressors; upon signaling, NotchIC is released, binds to CSL and activates transcription. Hedgehog pathway: in the absence of a signal, Cubitus Interruptus is cleaved to its repressor form; upon signaling, full-length Ci is produced and activates transcription. Hypoxia pathway: in normoxia, HIF1α is degraded; in hypoxia, HIF1α is stabilized, dimerizes with ARNT, binds to DNA and activates transcription.