The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation
Open accessAbstract
BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1+/−) developed one and often several BAP1−/− malignancies in their lifetime, mostly malignant mesothelioma, uveal melanoma, and so on. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity. The possible activity of BAP1 in the cytoplasm is unknown. Cells with reduced levels of BAP1 exhibit chromosomal abnormalities and decreased DNA repair by homologous recombination, indicating that BAP1 dosage is critical. Cells with extensive DNA damage should die and not grow into malignancies. Here we discover that BAP1 localizes at the endoplasmic reticulum. Here, it binds, deubiquitylates, and stabilizes type 3 inositol-1,4,5-trisphosphate receptor (IP3R3), modulating calcium (Ca2+) release from the endoplasmic reticulum into the cytosol and mitochondria, promoting apoptosis. Reduced levels of BAP1 in BAP1+/− carriers cause reduction both of IP3R3 levels and of Ca2+ flux, preventing BAP1+/− cells that accumulate DNA damage from executing apoptosis. A higher fraction of cells exposed to either ionizing or ultraviolet radiation, or to asbestos, survive genotoxic stress, resulting in a higher rate of cellular transformation. We propose that the high incidence of cancers in BAP1+/− carriers results from the combined reduced nuclear and cytoplasmic activities of BAP1. Our data provide a mechanistic rationale for the powerful ability of BAP1 to regulate gene–environment interaction in human carcinogenesis.
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Cites
Calcium's Role in Mechanotransduction during Muscle Development
Benavides Damm, T., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,502
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Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas
Harbour, J. W., Onken, M. D., Roberson, E. D. O., Duan, S., Cao, L., Worley, L. A., Council, M. L., Matatall, K. A., Helms, C., & Bowcock, A. M. (2010) · Science · doi:10.1126/science.1194472 · Cited by 1,462
Germline BAP1 Mutations Predispose to Malignant Mesothelioma
Testa, J. R., Cheung, M., Pei, J., Below, J. E., Tan, Y., Sementino, E., Cox, N. J., Dogan, A. U., Pass, H. I., Trusa, S., et al. (2011) · Nature Genetics · doi:10.1038/ng.912 · Cited by 1,076
Self-citationIsolation of mitochondria-associated membranes and mitochondria from animal tissues and cells
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Self-citationBAP1 loss defines a new class of renal cell carcinoma
Peña-Llopis, S., Vega-Rubín-de-Celis, S., Liao, A., Leng, N., Pavía-Jiménez, A., Wang, S., Yamasaki, T., Zhrebker, L., Sivanand, S., Spence, P., et al. (2012) · Nature Genetics · doi:10.1038/ng.2323 · Cited by 959
The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease
Berridge, M. J. (2016) · Physiological Reviews · doi:10.1152/physrev.00006.2016 · Cited by 753
Germline mutations in BAP1 predispose to melanocytic tumors
Wiesner, T., Obenauf, A. C., Murali, R., Fried, I., Griewank, K. G., Ulz, P., Windpassinger, C., Wackernagel, W., Loy, S., Wolf, I., et al. (2011) · Nature Genetics · doi:10.1038/ng.910 · Cited by 725
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BAP1 links metabolic regulation of ferroptosis to tumour suppression
Zhang, Y., Shi, J., Liu, X., Feng, L., Gong, Z., Koppula, P., Sirohi, K., Li, X., Wei, Y., Lee, H., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0178-0 · Cited by 1,013
Molecular mechanisms and consequences of mitochondrial permeability transition
Bonora, M., Giorgi, C., & Pinton, P. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00433-y · Cited by 538
Self-citationMitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases
(2018) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2018.05.006 · Cited by 455
Apoptotic cell death in disease—Current understanding of the NCCD 2023
Vitale, I., Pietrocola, F., Guilbaud, E., Aaronson, S. A., Abrams, J. M., Adam, D., Agostini, M., Agostinis, P., Alnemri, E. S., Altucci, L., et al. (2023) · Cell Death & Differentiation · doi:10.1038/s41418-023-01153-w · Cited by 361
Self-citationMesothelioma: Scientific clues for prevention, diagnosis, and therapy
Carbone, M., Adusumilli, P. S., Alexander, H. R., Baas, P., Bardelli, F., Bononi, A., Bueno, R., Felley‐Bosco, E., Galateau‐Salle, F., Jablons, D., et al. (2019) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21572 · Cited by 335
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Metadata
- Authors
- Bononi, A., Giorgi, C., Patergnani, S., Larson, D., Verbruggen, K., Tanji, M., Pellegrini, L., Signorato, V., Olivetto, F., Pastorino, S., Nasu, M., Napolitano, A., Gaudino, G., Morris, P., Sakamoto, G., Ferris, L. K., Danese, A., Raimondi, A., Tacchetti, C., Kuchay, S., Pass, H. I., Affar, E. B., Yang, H., Pinton, P., & Carbone, M.
- Venue
- Nature
- Published
- 2017-06
- Volume
- 546
- Issue
- 7659
- Pages
- 549-553
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2624817404
- Cited by
- 401
- References
- 43
- FWCI
- 26.73
- Type
- journal article
- Language
- en
- Open access
- green
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- Bononi, A., Giorgi, C., Patergnani, S., Larson, D., Verbruggen, K., Tanji, M., Pellegrini, L., Signorato, V., Olivetto, F., Pastorino, S., Nasu, M., Napolitano, A., Gaudino, G., Morris, P., Sakamoto, G., Ferris, L. K., Danese, A., Raimondi, A., Tacchetti, C., . . . Carbone, M. (2017). BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Nature. https://doi.org/10.1038/nature22798
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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
