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Conversion of Bcl-2 from Protector to Killer by Interaction with Nuclear Orphan Receptor Nur77/TR3
Open accessAbstract
The Bcl-2 family proteins are key regulators of apoptosis in human diseases and cancers. Though known to block apoptosis, Bcl-2 promotes cell death through an undefined mechanism. Here, we show that Bcl-2 interacts with orphan nuclear receptor Nur77 (also known as TR3), which is required for cancer cell apoptosis induced by many antineoplastic agents. The interaction is mediated by the N-terminal loop region of Bcl-2 and is required for Nur77 mitochondrial localization and apoptosis. Nur77 binding induces a Bcl-2 conformational change that exposes its BH3 domain, resulting in conversion of Bcl-2 from a protector to a killer. These findings establish the coupling of Nur77 nuclear receptor with the Bcl-2 apoptotic machinery and demonstrate that Bcl-2 can manifest opposing phenotypes, induced by interactions with proteins such as Nur77, suggesting novel strategies for regulating apoptosis in cancer and other diseases.
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Citations
Cited by
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Fulda, S., & Debatin, K.-M. (2006) · Oncogene · doi:10.1038/sj.onc.1209608 · Cited by 2,312
Redox regulation of cell survival
Trachootham, D., Lu, W., Ogasawara, M. A., Valle, N. R.-D., & Huang, P. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1957 · Cited by 1,781
Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes
Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C. B., & Tsujimoto, Y. (2004) · Nature Cell Biology · doi:10.1038/ncb1192 · Cited by 1,358
Cytoplasmic functions of the tumour suppressor p53
Green, D. R., & Kroemer, G. (2009) · Nature · doi:10.1038/nature07986 · Cited by 1,106
Metadata
- Authors
- Lin, B., Kolluri, S. K., Lin, F., Liu, W., Han, Y.-H., Cao, X., Dawson, M. I., Reed, J. C., & Zhang, X.-K.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 116
- Issue
- 4
- Pages
- 527-540
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2155235678
- Cited by
- 671
- References
- 0
- FWCI
- 15.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Conversion of Bcl-2 from Protector to Killer by Interaction with Nuclear Orphan Receptor Nur77/TR3. https://app.cochat.ai/papers/10.1016/s0092-8674(04)00162-x
- The paper
- Lin, B., Kolluri, S. K., Lin, F., Liu, W., Han, Y.-H., Cao, X., Dawson, M. I., Reed, J. C., & Zhang, X.-K. (2004). Conversion of Bcl-2 from Protector to Killer by Interaction with Nuclear Orphan Receptor Nur77/TR3. Cell. https://doi.org/10.1016/s0092-8674(04)00162-x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
