Caspase 2-mediated tumor suppression involves survivin gene silencing

Abstract

One of the pivotal functions of endogenous tumor suppression is to oppose aberrant cell survival, but the molecular requirements of this process are not completely understood. Here, we show that caspase 2, a death effector with largely unknown functions, represses transcription of the survivin gene, a general regulator of cell division and cytoprotection in tumors. This pathway involves caspase 2 proteolytic cleavage of the NFκB activator, RIP1. In turn, loss of RIP1 abolishes transcription of NFκB target genes, including survivin, resulting in deregulated mitotic transitions, enhanced apoptosis, and suppression of tumorigenicity, in vivo. Therefore, caspase 2 functions as an endogenous inhibitor of NFκB-dependent cell survival, and this mechanism may contribute to tumor suppression in humans.