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Abstract
Through global profiling of genes that were expressed soon after p53 expression, we
identified a novel gene termed PUMA (p53 upregulated modulator of apoptosis). The
protein encoded by PUMA was found to be exclusively mitochondrial and to bind to Bcl-2
and Bcl-X(L) through a BH3 domain. Exogenous expression of PUMA resulted in an extremely
rapid and profound apoptosis that occurred much earlier than that resulting from exogenous
expression of p53. Based on its unique expression patterns, p53 dependence, and biochemical
properties, PUMA may be a direct mediator of p53-associated apoptosis.