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Cellular & Molecular Biology Letters

Open Access

Puma, a critical mediator of cell death — one decade on from its discovery

Cellular & Molecular Biology LettersAn International Journal201217:32

Received: 19 March 2012

Accepted: 7 September 2012

Published: 20 September 2012


PUMA (p53 upregulated modulator of apoptosis) is a pro-apoptotic member of the BH3-only subgroup of the Bcl-2 family. It is a key mediator of p53-dependent and p53-independent apoptosis and was identified 10 years ago. The PUMA gene is mapped to the long arm of chromosome 19, a region that is frequently deleted in a large number of human cancers. PUMA mediates apoptosis thanks to its ability to directly bind known anti-apoptotic members of the Bcl-2 family. It mainly localizes to the mitochondria. The binding of PUMA to the inhibitory members of the Bcl-2 family (Bcl-2-like proteins) via its BH3 domain seems to be a critical regulatory step in the induction of apoptosis. It results in the displacement of the proteins Bax and/or Bak. This is followed by their activation and the formation of pore-like structures on the mitochondrial membrane, which permeabilizes the outer mitochondrial membrane, leading to mitochondrial dysfunction and caspase activation. PUMA is involved in a large number of physiological and pathological processes, including the immune response, cancer, neurodegenerative diseases and bacterial and viral infections.

Key words

Apoptosis BH3-only proteinsCarcinogenesisInhibitory members of the Bcl-2 familyIntrinsic apoptosis pathwayp53Pro-apoptotic members of Bcl-2 familyPUMAPost-translational regulationTranscription factors