Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis
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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Quantitative proteomic analysis of protein expression changes conferred by asukamycin treatment in 231MFP cells showed many known p53 transcriptional targets upregulated, including GADD45A, GADD45B, ANKRD1, HMOX1, ATF3, PMAIP1, DDIT4, DNAJB9, and PLK2.
“quantitative proteomic analysis of protein expression changes conferred by asukamycin treatment in 231MFP cells showed many known p53 transcriptional targets upregulated in expression, including GADD45A, GADD45B, ANKRD1, HMOX1, ATF3, PMAIP1, DDIT4, DNAJB9, and PLK2 (Extended Data Figure 9) 31–37.”
From Manumycin polyketides act as molecular glues between UBR7 and P53 (2020) · cites this paper as [33]
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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
- Venue
- Science
- Published
- 2000-05-12
- Volume
- 288
- Issue
- 5468
- Pages
- 1053-1058
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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