Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: p85alpha acts as a novel signal transducer for mediation of cellular apoptotic response to UV radiation.

Authors: Song, Lun; Li, Jingxia; Ye, Jianping; Yu, Gang; Ding, Jin; Zhang, Dongyun; Ouyang, Weiming; Dong, Zigang; Kim, Sung O; Huang, Chuanshu

Published In Mol Cell Biol, (2007 Apr)

Abstract: Apoptosis is an important cellular response to UV radiation (UVR), but the corresponding mechanisms remain largely unknown. Here we report that the p85alpha regulatory subunit of phosphatidylinositol 3-kinase (PI-3K) exerted a proapoptotic role in response to UVR through the induction of tumor necrosis factor alpha (TNF-alpha) gene expression. This special effect of p85alpha was unrelated to the PI-3K-dependent signaling pathway. Further evidence demonstrated that the inducible transcription factor NFAT3 was the major downstream target of p85alpha for the mediation of UVR-induced apoptosis and TNF-alpha gene transcription. p85alpha regulated UVR-induced NFAT3 activation by modulation of its nuclear translocation and DNA binding and the relevant transcriptional activities. Gel shift assays and site-directed mutagenesis allowed the identification of two regions in the TNF-alpha gene promoter that served as the NFAT3 recognition sequences. Chromatin immunoprecipitation assays further confirmed that the recruitment of NFAT3 to the endogenous TNF-alpha promoter was regulated by p85alpha upon UVR exposure. Finally, the knockdown of the NFAT3 level by its specific small interfering RNA decreased UVR-induced TNF-alpha gene transcription and cell apoptosis. The knockdown of endogenous p85alpha blocked NFAT activity and TNF-alpha gene transcription, as well as cell apoptosis. Thus, we demonstrated p85alpha-associated but PI-3K-independent cell death in response to UVR and identified a novel p85alpha/NFAT3/TNF-alpha signaling pathway for the mediation of cellular apoptotic responses under certain stress conditions such as UVR.

PubMed ID: 17242187 Exiting the NIEHS site

MeSH Terms: Active Transport, Cell Nucleus; Animals; Apoptosis*; Cell Nucleus/metabolism; Cells, Cultured; Fibroblasts/metabolism; Gene Expression Regulation; Mice; Mice, Knockout; Mutagenesis, Site-Directed; Mutation; NFATC Transcription Factors/genetics; NFATC Transcription Factors/physiology*; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/physiology*; Promoter Regions, Genetic; Protein Subunits/genetics; Protein Subunits/physiology; Signal Transduction; Tumor Necrosis Factor-alpha/genetics; Tumor Necrosis Factor-alpha/physiology*; Ultraviolet Rays*

Back
to Top