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

Cellular & Molecular Biology Letters volume 17, pages 646–669 (2012)Cite this article

Abstract

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.

Abbreviations

ADI/II:

activation domain I/II

Apaf-1:

apoptosis protease activating factor-1

Bad:

Bcl-2 associated death promoter

Bak:

Bcl-2 antagonist killer

Bax:

Bcl-2 associated protein x

Bcl-2:

B-cell leukemia/lymphoma-2

BH1-4:

Bcl-2 homology domains 1-4

Bid:

BH3 interacting domain death agonist

Bik:

Bcl-2 interacting killer

Bim:

Bcl-2 interacting mediator of cell death

Bmf:

Bcl-2 modifying factor

Bod:

Bcl-2-related ovarian death gene

Bok:

Bcl-2 ovarian killer

BS1/2:

p53 binding site 1/2

CHOP:

C/EBP homologous protein

DEN:

diethylnitrosamine

GSK-3:

glycogen synthase kinase-3

HRK:

harakiri, activator of apoptosis

HSPCs:

hematopoietic stem/progenitor cells

HSV-1:

human herpes virus

IKK:

IκB kinase

IL-3:

interleukin 3

Lys:

lysine

Mcl-1:

myeloid cell leukemia-1

MEFs:

mouse embryo fibroblasts

miRNA/miR:

microRNA

MLS:

mitochondrial localization signal

MOMP:

mitochondrial outer membrane permeabilization

NOXA (PMAP1):

phorbol-12-myristate-13-acetate-induced protein 1

OMM:

outer mitochondrial membrane

PCD:

programmed cell death

PI3K:

phosphoinositide 3-kinase

PUMA:

p53 upregulated modulator of apoptosis

ROS:

reactive oxygen species

Ser:

serine

Smac/DIABLO:

second mitochondria-derived activator or caspases/direct IAP binding protein with low pI

TRB3:

tribbles 3 homolog

UV-γIR:

ultraviolet-gamma irradiation

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Authors and Affiliations

  1. Department of Thermobiology, University of łódź, ul. Pomorska 141/143, 90-236, łódź, Poland

    Paweł Hikisz

  2. Department of Cytobiochemistry, University of łódź, ul. Pomorska 141/143, 90-236, łódź, Poland

    Zofia M. Kiliańska

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  1. Paweł Hikisz
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  2. Zofia M. Kiliańska
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Correspondence to Zofia M. Kiliańska.

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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

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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