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NF-κB-mediated repression of growth arrest- and DNA-damage-inducible proteins 45α and γ is essential for cancer cell survival
Abstract
The NF-κB/IκB signaling pathway is a critical regulator of cell survival in cancer. Here, we report that combined down-regulation of growth arrest- and DNA-damage-inducible proteins (GADD)45α and γ expression by NF-κB is an essential step for various cancer types to escape programmed cell death. We demonstrate that inhibition of NF-κB in cancer cells results in GADD45α- and γ-dependent induction of apoptosis and inhibition of tumor growth. Inhibition of GADD45α and γ in cancer cells by small interfering RNA abrogates apoptosis induction by the inhibitor of NF-κB and blocks c-Jun N-terminal kinase activation, whereas overexpression of GADD45α and γ activates c-Jun N-terminal kinase and induces apoptosis. These results establish an unambiguous role for the GADD45 family as an essential mediator of cell survival in cancer cells with implications for cancer chemotherapy and novel drug discovery.
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“c-Myc suppresses GADD45g gene expression in prostate cancer cells37,38.”
From Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms (2024) · cites this paper as [38]
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Cited by
Human-specific loss of regulatory DNA and the evolution of human-specific traits
McLean, C. Y., Reno, P. L., Pollen, A. A., Bassan, A. I., Capellini, T. D., Guenther, C., Indjeian, V. B., Lim, X., Menke, D. B., Schaar, B. T., et al. (2011) · Nature · doi:10.1038/nature09774 · Cited by 535
Skin-Resident T Cells Sense Ultraviolet Radiation–Induced Injury and Contribute to DNA Repair
MacLeod, A. S., Rudolph, R., Corriden, R., Ye, I., Garijo, O., & Havran, W. L. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1303297 · Cited by 77
Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms
Zhang, P., You, N., Ding, Y., Zhu, W., Wang, N., Xie, Y., Huang, W., Ren, Q., Qin, T., Fu, R., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47297-2 · Cited by 11
Metadata
- Authors
- Zerbini, L. F., Wang, Y., Czibere, A., Correa, R. G., Cho, J.-Y., Ijiri, K., Wei, W., Joseph, M., Gu, X., Grall, F., Goldring, M. B., Zhou, J.-R., & Libermann, T. A.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-09-07
- Volume
- 101
- Issue
- 37
- Pages
- 13618-13623
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 129
- References
- 3
- Language
- en
- Update notices
- correction (2004-10-19)
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- Zerbini, L. F., Wang, Y., Czibere, A., Correa, R. G., Cho, J.-Y., Ijiri, K., Wei, W., Joseph, M., Gu, X., Grall, F., Goldring, M. B., Zhou, J.-R., & Libermann, T. A. (2004). NF-κB-mediated repression of growth arrest- and DNA-damage-inducible proteins 45α and γ is essential for cancer cell survival. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0402069101
