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

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

doi:10.1038/sj.onc.1207057

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

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

Research output: Contribution to journal › Article › peer-review

106 Citations (Scopus)

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.

Original language	English
Pages (from-to)	8931-8938
Number of pages	8
Journal	Oncogene
Volume	22
Issue number	55
DOIs	https://doi.org/10.1038/sj.onc.1207057
Publication status	Published - Dec 4 2003
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/sj.onc.1207057

Cite this

@article{6b7af2c93cc54e6e86a938e1cc7e2090,

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.",

author = "Aglipay, {Jason A.} and Lee, {Sam W.} and Shinya Okada and Nobuko Fujiuchi and Takao Ohtsuka and Kwak, {Jennifer C.} and Yi Wang and Johnstone, {Ricky W.} and Chuxia Deng and Jun Qin and Toru Ouchi",

note = "Funding Information: We are grateful to Drs David M Livingston and George R Stark for helpful discussion, Ralph Scully for HCC1937-BRCA1 cells, Mutsuko Ouchi for generating and characterizing anti-BRCA1 monoclonal antibodies, Dr Scott Henderson, Jane Sue and Bryan Kloos for confocal laser microscope analysis, and the Mount Sinai School of Medicine Core Facilities for the monoclonal antibody, DNA sequencing and microscopic analysis. This work was supported by an NIH Predoctoral Training Award (JAA), the New York City Council Speaker{\textquoteright}s Fund (TO), an EMPIRE Grant of State of New York (TO) and National Cancer Institute Awards CA80058, CA78356 (SWL), CA84199 (JQ) and CA79892 and CA90631 (TO).",

year = "2003",

month = dec,

day = "4",

doi = "10.1038/sj.onc.1207057",

language = "English",

volume = "22",

pages = "8931--8938",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "55",

}

TY - JOUR

T1 - A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway

AU - Aglipay, Jason A.

AU - Lee, Sam W.

AU - Okada, Shinya

AU - Fujiuchi, Nobuko

AU - Ohtsuka, Takao

AU - Kwak, Jennifer C.

AU - Wang, Yi

AU - Johnstone, Ricky W.

AU - Deng, Chuxia

AU - Qin, Jun

AU - Ouchi, Toru

N1 - Funding Information: We are grateful to Drs David M Livingston and George R Stark for helpful discussion, Ralph Scully for HCC1937-BRCA1 cells, Mutsuko Ouchi for generating and characterizing anti-BRCA1 monoclonal antibodies, Dr Scott Henderson, Jane Sue and Bryan Kloos for confocal laser microscope analysis, and the Mount Sinai School of Medicine Core Facilities for the monoclonal antibody, DNA sequencing and microscopic analysis. This work was supported by an NIH Predoctoral Training Award (JAA), the New York City Council Speaker’s Fund (TO), an EMPIRE Grant of State of New York (TO) and National Cancer Institute Awards CA80058, CA78356 (SWL), CA84199 (JQ) and CA79892 and CA90631 (TO).

PY - 2003/12/4

Y1 - 2003/12/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=9144269673&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9144269673&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1207057

DO - 10.1038/sj.onc.1207057

M3 - Article

C2 - 14654789

AN - SCOPUS:9144269673

SN - 0950-9232

VL - 22

SP - 8931

EP - 8938

JO - Oncogene

JF - Oncogene

IS - 55

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this