Although a previous study showed that in response to neurotrophin signaling, NGFR might mediate p53-dependent neuron cell death by activating the JNK pathway (Aloyz et al., 1998), our studies as presented here unveil a novel nuclear function of this membrane receptor, i.e., to promote cancer cell proliferation and survival by directly inhibiting p53 transcriptional activity and indirectly destabilizing p53 protein via MDM2. The gene discussed is MDM2; the disease is cancer.