Caspase 2-mediated tumor suppression involves survivin gene silencing.

Oncogene
M GuhaD C Altieri

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 nuclear factor kappaB (NFkappaB) activator, RIP1. In turn, loss of RIP1 abolishes transcription of NFkappaB 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 NFkappaB-dependent cell survival and this mechanism may contribute to tumor suppression in humans.

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Methods Mentioned

BETA
PCR
fluorescence microscopy
flow cytometry
nucleic acid purification
light microscopy
transfection
flow
xenograft

Software Mentioned

Prism
GraphPad

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