A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1
Open accessAbstract
DNA damage-activated nuclease identified: Cells that experience stresses and accumulate excessive damage to DNA undergo cell death mediated by a nuclear enzyme known as PARP-1. During this process, apoptosis-inducing factor (AIF) translocates to the nucleus and activates one or more nucleases to cleave DNA. Wang et al. found that macrophage migration inhibitory factor (MIF) is an AIF-associated endonuclease that contributes to PARP-1-induced DNA fragmentation (see the Perspective by Jonas). In mouse neurons in culture, loss of MIF protected neurons from cell death caused by excessive stimulation. Targeting MIF could thus provide a therapeutic strategy against diseases in which PARP-1 activation is excessive. Science , this issue p. 82 ; see also p. 36
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MIF has emerged as the main nuclease precipitating parthanatos in a recent screening for AIF-binding proteins.
“Macrophage migration inhibitory factor (MIF) has emerged as the main nuclease precipitating parthanatos in a recent screening for AIF-binding proteins [679].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [679]
Cytosolic AIF promotes translocation of MIF into nucleus, where MIF precipitates parthanatos by catalyzing DNA cleavage.
“cytosolic AIF reportedly promotes the translocation of MIF into the nucleus, where MIF precipitates parthanatos by catalyzing DNA cleavage.”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [679]
MIF depletion or specific mutations in its nuclease domain confer protection against parthanatos in vitro and in vivo in an experimental model of focal cerebral ischemia.
“MIF depletion or specific mutations in its nuclease domain confer protection against parthanatos in vitro and in vivo (in an experimental model of focal cerebral ischemia) [679].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [679]
Cites
Mediation of Poly(ADP-Ribose) Polymerase-1-Dependent Cell Death by Apoptosis-Inducing Factor
Yu, S.-W., Wang, H., Poitras, M. F., Coombs, C., Bowers, W. J., Federoff, H. J., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2002) · Science · doi:10.1126/science.1072221 · Cited by 1,826 · see citing works
Self-citationMEME-ChIP: motif analysis of large DNA datasets
Machanick, P., & Bailey, T. L. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr189 · Cited by 1,815 · see citing works
Identifying ChIP-seq enrichment using MACS
Feng, J., Liu, T., Qin, B., Zhang, Y., & Liu, X. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.101 · Cited by 1,805 · see citing works
Macrophage migration inhibitory factor: a regulator of innate immunity
Calandra, T., & Roger, T. (2003) · Nature reviews. Immunology · doi:10.1038/nri1200 · Cited by 1,782 · see citing works
Structure of a B-DNA dodecamer: conformation and dynamics.
Drew, H. R., Wing, R. M., Takano, T., Broka, C. A., Tanaka, S., Itakura, K., & Dickerson, R. E. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.4.2179 · Cited by 1,562 · see citing works
Protection from septic shock by neutralization of macrophage migration inhibitory factor
Calandra, T., Echtenacher, B., Roy, D. L., Pugin, J., Metz, C. N., Hültner, L., Heumann, D., Männel, D. N., Bucala, R., & Glauser, M. P. (2000) · Nature Medicine · doi:10.1038/72262 · Cited by 724 · see citing works
Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death
Yu, S.-W., Andrabi, S. A., Wang, H., Kim, N. S., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606528103 · Cited by 718 · see citing works
Self-citationRole of poly(ADP-ribose) synthetase in inflammation and ischaemia–reperfusion
Szabó, C., & Dawson, V. L. (1998) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(98)01193-6 · Cited by 685 · see citing works
Self-citationHexServer: an FFT-based protein docking server powered by graphics processors
Macindoe, G., Mavridis, L., Venkatraman, V., Devignes, M., & Ritchie, D. W. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq311 · Cited by 674 · see citing works
A Proinflammatory Cytokine Inhibits P53 Tumor Suppressor Activity
Hudson, J. D., Shoaibi, M. A., Maestro, R., Carnero, A., Hannon, G. J., & Beach, D. H. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.10.1375 · Cited by 649 · see citing works
Parthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities
Fatokun, A. A., Dawson, V. L., & Dawson, T. M. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12416 · Cited by 594 · see citing works
Self-citationIntracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1
Kleemann, R., Haußer, A., Geiger, G., Mischke, R., Burger‐Kentischer, A., Flieger, O., Johannes, F., Roger, T., Calandra, T., Kapurniotu, A., et al. (2000) · Nature · doi:10.1038/35041591 · Cited by 567 · see citing works
Wang, Y., Kim, N. S., Haince, J.-F., Kang, H. C., David, K. K., Andrabi, S. A., Poirier, G. G., Dawson, V. L., & Dawson, T. M. (2011) · Science Signaling · doi:10.1126/scisignal.2000902 · Cited by 476 · see citing works
Self-citationBiology of Poly(ADP-Ribose) Polymerases: The Factotums of Cell Maintenance
Bai, P. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.01.034 · Cited by 445 · see citing works
Poly(ADP-ribose) signals to mitochondrial AIF: A key event in parthanatos
Wang, Y., Dawson, V. L., & Dawson, T. M. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.03.020 · Cited by 405 · see citing works
Self-citationMechanisms of AIF-Mediated Apoptotic DNA Degradation in <i>Caenorhabditis elegans</i>
Wang, X., Yang, C., Chai, J., Shi, Y., & Xue, D. (2002) · Science · doi:10.1126/science.1076194 · Cited by 393 · see citing works
Hu, S., Xie, Z., Onishi, A., Yu, X., Jiang, L., Lin, J., Rho, H., Woodard, C. L., Wang, H., Jeong, J. S., et al. (2009) · Cell · doi:10.1016/j.cell.2009.08.037 · Cited by 377 · see citing works
Self-citationRole of the Peroxynitrite-Poly(ADP-Ribose) Polymerase Pathway in Human Disease
Pacher, P., & Szabó, C. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080019 · Cited by 364 · see citing works
Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor.
Sun, H., Bernhagen, J., Bucala, R., & Lolis, E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.11.5191 · Cited by 337 · see citing works
MacKay, C., Déclais, A., Lundin, C., Agostinho, A., Deans, A. J., Macartney, T., Hofmann, K., Gartner, A., West, S. C., Helleday, T., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.021 · Cited by 311 · see citing works
Lubetsky, J. B., Dios, A., Han, J., Aljabari, B., Ruzsicska, B. P., Mitchell, R. A., Lolis, E., & Al‐Abed, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203220200 · Cited by 306 · see citing works
Wang, H., Yu, S.-W., Koh, D. W., Lew, J., Coombs, C. M., Bowers, W. J., Federoff, H. J., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3461-04.2004 · Cited by 282 · see citing works
Self-citationAIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis
Candé, C., Vahsen, N., Kouranti, I., Schmitt, E., Daugas, É., Spahr, C. S., Luban, J., Kroemer, R. T., Giordanetto, F., Garrido, C., et al. (2004) · Oncogene · doi:10.1038/sj.onc.1207279 · Cited by 278 · see citing works
Poly(ADP-ribose) signaling in cell death
Virág, L., Robaszkiewicz, A., Rodriguez-Vargas, J. M., & Oliver, F. J. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.007 · Cited by 273 · see citing works
Kratz, K., Schöpf, B., Kaden, S., Sendoel, A., Eberhard, R., Lademann, C. A., Cannavò, E., Sartori, A. A., Hengartner, M. O., & Jiricny, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.022 · Cited by 271 · see citing works
The macrophage migration inhibitory factor MIF is a phenylpyruvate tautomerase
Rosengren, E., Åman, P., Thelin, S., et al. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01261-1 · Cited by 263 · see citing works
PARP-1 involvement in neurodegeneration: A focus on Alzheimer’s and Parkinson’s diseases
Martire, S., Mosca, L., & D’Erme, M. (2015) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2015.04.001 · Cited by 228 · see citing works
Artus, C., Boujrad, H., Bouharrour, A., Brunelle-Navas, M.-N., Hoos, S., Yuste, V. J., Lenormand, P., Rousselle, J.-C., Namane, A., England, P., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.43 · Cited by 220 · see citing works
Andrabi, S. A., Kang, H. C., Haince, J.-F., Lee, Y.-I., Zhang, J., Chi, Z., West, A. B., Koehler, R. C., Poirier, G. G., Dawson, T. M., et al. (2011) · Nature Medicine · doi:10.1038/nm.2387 · Cited by 216 · see citing works
Self-citationCrystal structure of the macrophage migration inhibitory factor from rat liver
Suzuki, M., Sugimoto, H., Nakagawa, A., Tanaka, I., Nishihira, J., & Sakai, M. (1996) · Nature Structural Biology · doi:10.1038/nsb0396-259 · Cited by 190 · see citing works
Sequence, structure and functional diversity of PD-(D/E)XK phosphodiesterase superfamily
Steczkiewicz, K., Muszewska, A., Kniżewski, Ł., Rychlewski, L., & Ginalski, K. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks382 · Cited by 178 · see citing works
D-dopachrome tautomerase (D-DT or MIF-2): Doubling the MIF cytokine family
Merk, M., Mitchell, R. A., Endres, S., & Bucala, R. (2012) · Cytokine · doi:10.1016/j.cyto.2012.03.014 · Cited by 178 · see citing works
Systematic evaluation of factors influencing ChIP-seq fidelity
Chen, Y., Negre, N. N., Li, Q., Mieczkowska, J. O., Slattery, M. G., Liu, T., Zhang, Y., Kim, T.-K., He, H. H., Zieba, J. T., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1985 · Cited by 164 · see citing works
MIF Expression in the Rat Brain: Implications for Neuronal Function
Bacher, M., Meinhardt, A., Lan, H. Y., Dhabhar, F. S., Mu, W., Metz, C. N., Chesney, J. A., Gemsa, D., Donnelly, T. M., Atkins, R. C., et al. (1998) · Molecular Medicine · doi:10.1007/bf03401919 · Cited by 162 · see citing works
Bendrat, K., Al‐Abed, Y., Callaway, D. J. E., et al. (1997) · Biochemistry · doi:10.1021/bi971153a · Cited by 153 · see citing works
Fingerle-Rowson, G., Kaleswarapu, D. R., Schlander, C., Kabgani, N., Brocks, T., Reinart, N., Busch, R. M., Schütz, A. K., Lue, H., Du, X., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01907-08 · Cited by 144 · see citing works
Protein docking using case‐based reasoning
Ghoorah, A. W., Devignes, M., Smaïl‐Tabbone, M., & Ritchie, D. W. (2013) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24433 · Cited by 136 · see citing works
Glascock, J. J., Osman, E. Y., Coady, T. H., Rose, F. F., Shababi, M., & Lorson, C. L. (2011) · Journal of Visualized Experiments · doi:10.3791/2968 · Cited by 121 · see citing works
Kosiński, J., Feder, M., & Bujnicki, J. M. (2005) · BMC Bioinformatics · doi:10.1186/1471-2105-6-172 · Cited by 112 · see citing works
Generation and Characterization of Endonuclease G Null Mice
Irvine, R. A., Adachi, N., Shibata, D. K., Cassell, G. D., Yu, K., Karanjawala, Z. E., Hsieh, C.-L., & Lieber, M. R. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.1.294-302.2005 · Cited by 111 · see citing works
EndoG is dispensable in embryogenesis and apoptosis
David, K. K., Sasaki, M., Yu, S.-W., Dawson, T. M., & Dawson, V. L. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401787 · Cited by 96 · see citing works
Self-citationInácio, A. R. L., Ruscher, K., Leng, L., Bucala, R., & Deierborg, T. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.194 · Cited by 95 · see citing works
Pingoud, V., Wende, W., Friedhoff, P., Reuter, M., Alves, J., Jeltsch, A., Mones, L., Fuxreiter, M., & Pingoud, A. M. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.08.011 · Cited by 68 · see citing works
Sugimoto, H., Suzuki, M., Nakagawa, A., et al. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00553-4 · Cited by 63 · see citing works
Human Macrophage Migration Inhibitory Factor
Kudrin, A., Scott, M., Martin, S. M., Chung, C., Donn, R. P., McMaster, A., Ellison, S. M., Ray, D. W., Ray, K. P., & Binks, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601103200 · Cited by 63 · see citing works
Laganeckas, M., Margelevičius, M., & Venclovas, Č. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq958 · Cited by 45 · see citing works
Glascock, J., Osman, E. Y., Coady, T. H., et al. (2011) · Journal of Visualized Experiments · doi:10.3791/2968-v · Cited by 28 · see citing works
Xu, Z., Zhang, J., David, K. K., Yang, Z.-J., Li, X., Dawson, T. M., Dawson, V. L., & Koehler, R. C. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00747.2009 · Cited by 20 · see citing works
Self-citationA Non-canonical DNA Structure Enables Homologous Recombination in Various Genetic Systems
Masuda-Ozawa, T., Ito, Y., Terada, T., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.043810 · Cited by 19 · see citing works
Molecular Dynamics of the Neuronal EF-Hand Ca2+-Sensor Caldendrin
Reddy, P. P., Raghuram, V., Hradsky, J., Spilker, C., Chakraborty, A., Sharma, Y., Mikhaylova, M., & Kreutz, M. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103186 · Cited by 16 · see citing works
Zhang, W., Li, L., Wang, J., An, L., Hu, X., Xie, J., Yan, R., Chen, S., & Zhao, S. (2014) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-014-0094-1 · Cited by 9 · see citing works
Self-citationEffects of 2′-O-Methyl Nucleotide Substitution on EcoRI Endonuclease Cleavage Activities
Zhao, G., Zhao, B., Tong, Z., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077111 · Cited by 9 · see citing works
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- Authors
- Wang, Y., An, R., Umanah, G. K., Park, H., Nambiar, K., Eacker, S. M., Kim, B., Bao, L., Harraz, M. M., Chang, C., Chen, R., Wang, J. E., Kam, T.-I., Jeong, J. S., Xie, Z., Neifert, S., Qian, J., Andrabi, S. A., Blackshaw, S., Zhu, H., Song, H., Ming, G.-L., Dawson, V. L., & Dawson, T. M.
- Affiliations
- Johns Hopkins University (US)
- Shanghai Medical College of Fudan University (CN)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Wang, Yingfei
- Dawson, Valina L.
- Dawson, Ted M.
- ORCID
- Venue
- Science
- Published
- 2016-10-07
- Volume
- 354
- Issue
- 6308
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5134926
- OpenAlex
- W2529744299
- Cited by
- 421
- References
- 52
- Citations by year
- 2026: 44 · 2025: 55 · 2024: 51 · 2023: 53 · 2022: 48 · 2021: 50 · 2020: 33 · 2019: 34 · 2018: 33 · 2017: 15 · 2016: 3
- FWCI
- 14.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association (AHA) National Scientist Development (12SDG11900071)
- University of Texas Southwestern Medical Center Department of Pathology Startup
- UT Rising Stars
- National Institute on Drug Abuse
- NIH (K99/R00 NS078049, DA000266)
- National Institute of Neurological Disorders and Stroke (R01 NS067525, R37 NS067525, NS38377)
- Neurodegenerative Diseases
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- macrophage migration inhibitory factor, PARP1, apoptosis-inducing factor, nuclease activity, DNA damage, cell death, glutamate excitotoxicity, mitochondrial apoptosis, therapeutic target
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Amino Acid Sequence, Animals, Base Sequence, Cell Nucleus, Chromatin, Deoxyribonucleases, DNA Damage, DNA, Single-Stranded, HeLa Cells, Humans, Macrophage Migration-Inhibitory Factors, Mitochondria, Mutation, Neurons, Nucleic Acid Conformation, Apoptosis, Mice, Knockout, Oxidative Stress, Glutamic Acid, Intramolecular Oxidoreductases, Catalytic Domain, Stroke, Active Transport, Cell Nucleus, Apoptosis Inducing Factor, Mice, DNA Cleavage, DNA Fragmentation
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