IFI16是吡喃蛋白家族的一员，是一种与BRCA1相关的新型蛋白，参与p53介导的凋亡途径。

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

作者信息

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

机构信息

The Derald H Ruttenberg Cancer Center, The Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.

出版信息

Oncogene. 2003 Dec 4;22(55):8931-8. doi: 10.1038/sj.onc.1207057.

DOI:10.1038/sj.onc.1207057

PMID:14654789

Abstract

We identified IFI16 as a BRCA1-associated protein involved in p53-mediated apoptosis. IFI16 contains the Pyrin/PAAD/DAPIN domain, commonly found in cell death-associated proteins. BRCA1 (aa 502-802) interacted with the IFI16 Pyrin domain (aa 1-130). We found that IFI16 was localized in the nucleoplasm and nucleoli. Clear nucleolar IFI16 localization was not observed in HCC1937 BRCA1 mutant cells, but reintroduction of wild-type BRCA1 restored IFI16 nuclear relocalization following IR (ionizing radiation). Coexpression of IFI16 and BRCA1 enhanced DNA damage-induced apoptosis in mouse embryonic fibroblasts from BRCA1 mutant mice expressing wild-type p53, although mutant IFI16 deficient in binding to BRCA1 did not induce apoptosis. Furthermore, tetracycline-induced IFI16 collaborated in inducing apoptosis when adenovirus p53 was expressed in DNA-damaged p53-deficient EJ cells. These results indicate a BRCA1-IFI16 role in p53-mediated transmission of DNA damage signals and apoptosis.

摘要

我们鉴定出IFI16是一种与BRCA1相关的蛋白，参与p53介导的细胞凋亡。IFI16含有Pyrin/PAAD/DAPIN结构域，常见于与细胞死亡相关的蛋白中。BRCA1（第502 - 802个氨基酸）与IFI16的Pyrin结构域（第1 - 130个氨基酸）相互作用。我们发现IFI16定位于核质和核仁。在HCC1937 BRCA1突变细胞中未观察到清晰的核仁IFI16定位，但重新引入野生型BRCA1可恢复电离辐射后IFI16的核重新定位。IFI16和BRCA1的共表达增强了来自表达野生型p53的BRCA1突变小鼠胚胎成纤维细胞中DNA损伤诱导的细胞凋亡，尽管缺乏与BRCA1结合能力的突变型IFI16不能诱导细胞凋亡。此外，当腺病毒p53在DNA损伤的p53缺陷型EJ细胞中表达时，四环素诱导的IFI16协同诱导细胞凋亡。这些结果表明BRCA1 - IFI16在p53介导的DNA损伤信号传递和细胞凋亡中发挥作用。