The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
PALB2 Interacts with KEAP1 To Promote NRF2 Nuclear Accumulation and Function
Open accessAbstract
PALB2/FANCN is mutated in breast and pancreatic cancers and Fanconi anemia (FA). It controls the intranuclear localization, stability, and DNA repair function of BRCA2 and links BRCA1 and BRCA2 in DNA homologous recombination repair and breast cancer suppression. Here, we show that PALB2 directly interacts with KEAP1, an oxidative stress sensor that binds and represses the master antioxidant transcription factor NRF2. PALB2 shares with NRF2 a highly conserved ETGE-type KEAP1 binding motif and can effectively compete with NRF2 for KEAP1 binding. PALB2 promotes NRF2 accumulation and function in the nucleus and lowers the cellular reactive oxygen species (ROS) level. In addition, PALB2 also regulates the rate of NRF2 export from the nucleus following induction. Our findings identify PALB2 as a regulator of cellular redox homeostasis and provide a new link between oxidative stress and the development of cancer and FA.
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Cites
Kobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7130-7139.2004 · Cited by 2,224
Zhang, D. D., & Hannink, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8137-8151.2003 · Cited by 1,480
Self-citationDysfunctional KEAP1–NRF2 Interaction in Non-Small-Cell Lung Cancer
Singh, A., Misra, V., Thimmulappa, R. K., Lee, H., Ames, S., Hoque, M. O., Herman, J. G., Baylin, S. B., Sidransky, D., Gabrielson, E., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030420 · Cited by 1,060
Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene
Jones, S., Hruban, R. H., Kamiyama, M., Borges, M., Zhang, X., Parsons, D. W., Lin, J. C.-H., Palmisano, E., Brune, K., Jaffee, E. M., et al. (2009) · Science · doi:10.1126/science.1171202 · Cited by 826
Tong, K. I., Katoh, Y., Kusunoki, H., Itoh, K., Tanaka, T., & Yamamoto, M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.8.2887-2900.2006 · Cited by 759 · cited 1×
“NRF2 has two different KEAP1 binding motifs, a DLG motif and an ETGE motif (9, 14, 32), Interestingly, KEAP1 forms a dimer in the cell, and one NRF2 molecule can bind both monomers— one with the DLG and the other with the ETGE motif (14, 32).”
BackgroundStructural basis for defects of Keap1 activity provoked by its point mutations in lung cancer
Padmanabhan, B., Tong, K. I., Ohta, T., Nakamura, Y., Scharlock, M., Ohtsuji, M., Kang, M.-I., Kobayashi, A., Yokoyama, S., & Yamamoto, M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.013 · Cited by 735 · cited 1×
“Therefore, we conclude that the ETGE motif of PALB2 directly interacts with the kelch domain of KEAP1 in a fashion similar to the NRF2(ETGE)-KEAP1 interaction (12, 19).”
BackgroundBiallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer
Reid, S., Schindler, D., Hanenberg, H., Barker, K., Hanks, S., Kalb, R., Neveling, K., Kelly, P., Seal, S., Freund, M., et al. (2007) · Nature Genetics · doi:10.1038/ng1947 · Cited by 642
Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling
Lo, S., Li, X., Henzl, M. T., Beamer, L. J., & Hannink, M. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601243 · Cited by 604 · cited 2×
“Therefore, we conclude that the ETGE motif of PALB2 directly interacts with the kelch domain of KEAP1 in a fashion similar to the NRF2(ETGE)-KEAP1 interaction (12, 19).”
BackgroundTwo-site substrate recognition model for the Keap1-Nrf2 system: A hinge and latch mechanism
Tong, K. I., Kobayashi, A., Katsuoka, F., & Yamamoto, M. (2006) · Biological Chemistry · doi:10.1515/bc.2006.164 · Cited by 473
Fanconi anemia is associated with a defect in the BRCA2 partner PALB2
Xia, B., Dorsman, J. C., Ameziane, N., de Vries, Y., Rooimans, M. A., Sheng, Q., Pals, G., Errami, A., Gluckman, E., Llera, J., et al. (2007) · Nature Genetics · doi:10.1038/ng1942 · Cited by 465
Self-citation
Cited by
NRF2, a Transcription Factor for Stress Response and Beyond
He, F., Ru, X., & Wen, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134777 · Cited by 1,820
NRF2 and the Hallmarks of Cancer
Rojo de la Vega, M., Chapman, E., & Zhang, D. D. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.022 · Cited by 1,672
Self-citationNrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130
RETRACTED ARTICLE: A mechanism for the suppression of homologous recombination in G1 cells
Orthwein, A., Noordermeer, S. M., Wilson, M. D., Landry, S., Enchev, R. I., Sherker, A., Munro, M., Pinder, J., Salsman, J., Dellaire, G., et al. (2015) · Nature · doi:10.1038/nature16142 · Cited by 471
Self-citationRetractedThe KEAP1–NRF2 System as a Molecular Target of Cancer Treatment
Taguchi, K., & Yamamoto, M. (2020) · Cancers · doi:10.3390/cancers13010046 · Cited by 195
“For instance, the following proteins have been reported as candidates: mitochondrial serine/threonine protein phosphatase PGAM family member 5 (PGAM5) [38], NFκB kinase inhibitor IKKβ (inhibitor of nuclear factor-kappa B kinase subunit β, referred to as IKBKB) [39], BRCA2 partner PALB2 (partner and localizer of BRCA2)…”
Background
Metadata
- Authors
- Ma, J., Cai, H., Wu, T., Sobhian, B., Huo, Y., Alcivar, A., Mehta, M., Cheung, K. L., Ganesan, S., Kong, A.-N. T., Zhang, D. D., & Xia, B.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2012-04-01
- Volume
- 32
- Issue
- 8
- Pages
- 1506-1517
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2098335512
- Cited by
- 192
- References
- 12
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- green
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- Ma, J., Cai, H., Wu, T., Sobhian, B., Huo, Y., Alcivar, A., Mehta, M., Cheung, K. L., Ganesan, S., Kong, A.-N. T., Zhang, D. D., & Xia, B. (2012). PALB2 Interacts with KEAP1 To Promote NRF2 Nuclear Accumulation and Function. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.06271-11
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