Faculty Opinions recommendation of PUMA is directly activated by NF-kappaB and contributes to TNF-alpha-induced apoptosis.
Year: 2009
Type: peer-review
Abstract: Tumor necrosis factor-α (TNF-α) is a cytokine that has an important role in immunity and inflammation by inducing cellular responses such as apoptosis.The transcription factor nuclear factor-κB (NF-κB) can paradoxically suppress and promote apoptosis in response to TNF-α.In this study, we found that p53 upregulated modulator of apoptosis (PUMA), a p53 downstream target and a BH3-only Bcl-2 family member, is directly regulated by NF-κB in response to TNF-α.TNF-α treatment led to increases in PUMA mRNA and protein levels in human colon cancer cells.The induction of PUMA was p53 independent, and mediated by the p65 component of NF-κB through a κB site in the PUMA promoter.The apoptotic effect of PUMA induction by TNF-α was unmasked by depleting the antiapoptotic protein Bcl-X L .In mice, PUMA was also induced by TNF-α in an NF-κB-dependent manner.TNF-α-induced apoptosis in a variety of tissues and cell types, including small intestinal epithelial cells, hepatocytes, and thymocytes, was markedly reduced in PUMAdeficient mice.Collectively, these results demonstrated that PUMA is a direct target of NF-κB and mediates TNF-α-induced apoptosis in vitro and in vivo.
Author: Douglas Green
Institution: St. Jude Children's Research Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4230183695