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