Cited by 2,112Cell death mechanisms and regulationCancer-related Molecular PathwaysHeat shock proteins research

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Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis

Oda, Eri, Ohki, Rieko, Murasawa, Hideki, Nemoto, Jiro, Shibue, Tsukasa, Yamashita, Toshiharu, Tokino, Takashi, Taniguchi, Tadatsugu, Tanaka, † Nobuyuki·2000·Science

DOI 10.1126/science.288.5468.1053

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Abstract

A critical function of tumor suppressor p53 is the induction of apoptosis in cells exposed to noxious stresses. We report a previously unidentified pro-apoptotic gene, Noxa . Expression of Noxa induction in primary mouse cells exposed to x-ray irradiation was dependent on p53. Noxa encodes a Bcl-2 homology 3 (BH3)–only member of the Bcl-2 family of proteins; this member contains the BH3 region but not other BH domains. When ectopically expressed, Noxa underwent BH3 motif–dependent localization to mitochondria and interacted with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9. We also demonstrate that blocking the endogenous Noxa induction results in the suppression of apoptosis. Noxa may thus represent a mediator of p53-dependent apoptosis.

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Authors: Oda, E., Ohki, R., Murasawa, H., Nemoto, J., Shibue, T., Yamashita, T., Tokino, T., Taniguchi, T., & Tanaka, †. N.
Affiliations: The University of Tokyo (JP)
Sapporo Medical University (JP)
Corresponding author: Oda, Eri
Ohki, Rieko
ORCID: Ohki, Rieko
Murasawa, Hideki
Shibue, Tsukasa
Tokino, Takashi
Taniguchi, Tadatsugu
Tanaka, † Nobuyuki
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2000-05-12
Volume: 288
Issue: 5468
Pages: 1053-1058
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.288.5468.1053
OpenAlex: W2024996523
Cited by: 2,112
References: 43
Citations by year: 2026: 21 · 2025: 36 · 2024: 51 · 2023: 56 · 2022: 44 · 2021: 62 · 2020: 65 · 2019: 71 · 2018: 59 · 2017: 67 · 2016: 76 · 2015: 77 · 2014: 73 · 2013: 83 · 2012: 89
FWCI: 39.09
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords: Noxa, BH3-only proteins, Bcl-2 family proteins, p53, X-ray irradiation, mitochondrial localization, caspase-9 activation, tumor suppressor
MeSH terms: Amino Acid Sequence, Animals, Cell Line, Cells, Cultured, DNA Damage, Enzyme Activation, Gene Expression Regulation, Humans, Mitochondria, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, RNA, Messenger, T-Lymphocytes, Tumor Suppressor Protein p53, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Amino Acid Substitution, Caspases, Amino Acid Motifs, Gene Expression Profiling, bcl-2-Associated X Protein, Mice, Caspase 9

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Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis

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