期刊
ONCOGENE
卷 27, 期 -, 页码 S71-S83出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.45
关键词
PUMA; BH3 domain; Bcl-2 family; p53; apoptosis
资金
- NIH [CA106348, CA121105]
- American Cancer Society [RSG-07-156-01-CNE]
- American Lung Association (LZ) [CA129829, P50CA097190]
- (Head and Neck Cancer SPORE Career Development Award) [U19A1068021]
- University of Pittsburgh Center for Medical Countermeasures Against Radiation Developmental Research Program
- Hillman Foundation, Alliance for Cancer Gene Therapy (ACGT)
- Flight Attendant Medical Research Institute (FAMRI)
- NATIONAL CANCER INSTITUTE [R01CA129829, P50CA097190, R01CA121105, R01CA106348] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [U01DK085570] Funding Source: NIH RePORTER
PUMA (p53 upregulated modulator of apoptosis) is a Bcl2 homology 3 (BH3)-only Bcl-2 family member and a critical mediator of p53-dependent and -independent apoptosis induced by a wide variety of stimuli, including genotoxic stress, deregulated oncogene expression, toxins, altered redox status, growth factor/cytokine withdrawal and infection. It serves as a proximal signaling molecule whose expression is regulated by transcription factors in response to these stimuli. PUMA transduces death signals primarily to the mitochondria, where it acts indirectly on the Bcl-2 family members Bax and/or Bak by relieving the inhibition imposed by antiapoptotic members. It directly binds and antagonizes all known antiapoptotic Bcl-2 family members to induce mitochondrial dysfunction and caspase activation. PUMA ablation or inhibition leads to apoptosis deficiency underlying increased risks for cancer development and therapeutic resistance. Although elevated PUMA expression elicits profound chemo- and radio-sensitization in cancer cells, inhibition of PUMA expression may be useful for curbing excessive cell death associated with tissue injury and degenerative diseases. Therefore, PUMA is a general sensor of cell death stimuli and a promising drug target for cancer therapy and tissue damage. Oncogene (2009) 27, S71-S83; doi: 10.1038/onc.2009.45
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