A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway

Aglipay, Jason A.; Lee, Sam W.; Okada, Shinya; Fujiuchi, Nobuko; Ohtsuka, Takao; Kwak, Jennifer C.; Wang, Yi; Johnstone, Ricky W.; Deng, Chu‐Xia; Qin, Jun; Ouchi, Toru

doi:10.1038/sj.onc.1207057

Cited by 116 publications

(95 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, IFI16 can also interact directly in vivo with the gene promoter region of both p53 and c-myc [22]. IFI16 has also been shown to bind BRCA1 and this complex has been reported to be involved in the p53-mediated cell death pathway, suggesting that IFI16 may play a role in DNA damage induced apoptosis [23]. However, IFI16 has also been shown to associate with the retinoblastoma tumour-suppressor protein Rb and the transcription factor E2F1, resulting in the inhibition of Rb-E2F1 mediated transcriptional repression [24].…”

Section: Early Research On the Human Pyhinsmentioning

confidence: 99%

The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease

Connolly

Bowie

2014

Biochemical Pharmacology

View full text Add to dashboard Cite

Section: Early Research On the Human Pyhinsmentioning

confidence: 99%

The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease

Connolly

Bowie

2014

Biochemical Pharmacology

View full text Add to dashboard Cite

“…As shown in Fig. 5B, treatment of cells with TSA resulted in increased cleavage of poly(ADP-ribose) polymerase (PARP) protein, which is indicative of caspasemediated apoptosis of cells (31). Consistent with these observations, fluorescence-activated cell sorting analyses of propidium iodide -stained control and TSA-treated LNCaP cells, which resulted in up-regulation of IFI16 protein and down-regulation of AR protein, revealed that TSA treatment significantly increased apoptosis of cells (Fig.…”

Section: Up-regulation Of Ifi16 In Lncap Cells Down-regulates Ar Exprmentioning

confidence: 99%

IFI16 in Human Prostate Cancer

Alimirah

Chen

Davis

et al. 2007

Molecular Cancer Research

View full text Add to dashboard Cite

Increased expression of IFI16 protein (encoded by the IFI16 gene) in normal human prostate epithelial cells is associated with cellular senescence-associated cell growth arrest. Consistent with a role for IFI16 protein in cellular senescence, the expression of IFI16 protein is either very low or not detectable in human prostate cancer cell lines. We now report that treatment of DU-145 and LNCaP prostate cancer cell lines with histone deacetylase inhibitor trichostatin A (TSA) or CGK1026 resulted in transcriptional activation of the IFI16 gene.

show abstract

“…The IFI16 protein binds to the COOH terminus (amino acids 362-393) of p53 (27) and overexpression of the IFI16 protein in cells increases p53 protein levels and stimulates the p53-mediated transcription (25,38). Conversely, knockdown of IFI16 expression results in down-regulation of p53 levels (25).…”

Section: Ifi16 Is a Transcriptional Target Of P53mentioning

confidence: 99%

Expression of an IFN-Inducible Cellular Senescence Gene, IFI16, Is Up-Regulated by p53

Song

Alimirah

Panchanathan

et al. 2008

Molecular Cancer Research

View full text Add to dashboard Cite

IFN-inducible IFI16 protein (encoded by IFI16 gene at 1q23.1) is the human member of the IFN-inducible structurally related p200 family proteins. Increased expression of the IFI16 protein, a positive modulator of p53-mediated transcription, in normal old human diploid fibroblasts (HDF) is associated with cellular senescence-mediated cell growth arrest. However, the underlying mechanisms that contribute to transcriptional activation of the IFI16 gene in old HDFs remain to be elucidated. Here, we reported that functional activation of p53 in normal young HDFs and p53-null Saos2 cell line resulted in transcriptional activation of the IFI16 gene. We identified a potential p53 DNA-binding site (indicated as IFI16-p53-BS) in the 5 ¶-regulatory region of the IFI16 gene. Importantly, p53 bound to IFI16-p53-BS in a sequence-specific manner in gel-mobility shift assays. Furthermore, p53 associated with the 5 ¶-regulatory region of the IFI16 gene in chromatin immunoprecipitation assays. Interestingly, p53 associated with the regulatory region of the IFI16 gene only on treatment of cells with DNA-damaging agents or in the old, but not in the young, HDFs. Importantly, our promoter-reporter assays, which were coupled with site-directed mutagenesis of IFI16-p53-BS, showed that p53 activates transcription of the IFI16 gene in HDFs through the p53 DNA-binding site. Together, our observations provide support for the idea that up-regulation of IFI16 expression by p53 and functional interactions between IFI16 protein and p53 contribute to cellular senescence.

show abstract

A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway

Cited by 116 publications

References 33 publications

The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease

The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease

IFI16 in Human Prostate Cancer

Expression of an IFN-Inducible Cellular Senescence Gene, IFI16, Is Up-Regulated by p53

Contact Info

Product

Resources

About