title: A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway.
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.
authors.affiliation: The Derald H Ruttenberg Cancer Center, The Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Aglipay
authors.forename: Sam W
authors.initials: SW
authors.lastname: Lee
authors.forename: Shinya
authors.initials: S
authors.lastname: Okada
authors.forename: Nobuko
authors.initials: N
authors.lastname: Fujiuchi
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Kwak
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Ricky W
authors.initials: RW
authors.lastname: Johnstone
authors.forename: Chuxia
authors.initials: C
authors.lastname: Deng
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.forename: Toru
authors.initials: T
authors.lastname: Ouchi
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D019313:BRCA1 Protein / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C489664:Ifi16 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D016159:Tumor Suppressor Protein p53; C076700:IFI16 protein, human