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

Cellular & Molecular Biology Letters

Zofia M. Kiliańska¹  Paweł Hikisz² 

[1] Department of Cytobiochemistry, University of łódź, łódź, Poland$$;Department of Thermobiology, University of łódź, łódź, Poland$$

关键词: Apoptosis;    Carcinogenesis;    Inhibitory members of the Bcl-2 family;    Intrinsic apoptosis pathway;    p53;    Pro-apoptotic members of Bcl-2 family;    PUMA;    Post-translational regulation;    Transcription factors;   

DOI  :  10.2478/s11658-012-0032-5

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

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.

【 授权许可】

Unknown