Puma, a critical mediator of cell death — one decade on from its discovery
Cellular & Molecular Biology Letters volume 17, pages 646–669 (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.
activation domain I/II
apoptosis protease activating factor-1
Bcl-2 associated death promoter
Bcl-2 antagonist killer
Bcl-2 associated protein x
Bcl-2 homology domains 1-4
BH3 interacting domain death agonist
Bcl-2 interacting killer
Bcl-2 interacting mediator of cell death
Bcl-2 modifying factor
Bcl-2-related ovarian death gene
Bcl-2 ovarian killer
p53 binding site 1/2
C/EBP homologous protein
glycogen synthase kinase-3
harakiri, activator of apoptosis
hematopoietic stem/progenitor cells
human herpes virus
myeloid cell leukemia-1
mouse embryo fibroblasts
mitochondrial localization signal
mitochondrial outer membrane permeabilization
- NOXA (PMAP1):
phorbol-12-myristate-13-acetate-induced protein 1
outer mitochondrial membrane
programmed cell death
p53 upregulated modulator of apoptosis
reactive oxygen species
second mitochondria-derived activator or caspases/direct IAP binding protein with low pI
tribbles 3 homolog
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Hikisz, P., Kiliańska, Z.M. Puma, a critical mediator of cell death — one decade on from its discovery. Cell Mol Biol Lett 17, 646–669 (2012). https://doi.org/10.2478/s11658-012-0032-5
- BH3-only proteins
- Inhibitory members of the Bcl-2 family
- Intrinsic apoptosis pathway
- Pro-apoptotic members of Bcl-2 family
- Post-translational regulation
- Transcription factors