Intersection of Redox Chemistry and Ubiquitylation: Post-Translational Modifications Required for Maintaining Cellular Homeostasis and Neuroprotection
Abstract
1. Introduction
2. Protecting and Maintaining Homeostasis within the Central Nervous System
3. Neuroprotection through Redox Chemistry
4. Interplay between the Ubiquitin-Proteasome System and ROS Production
4.1. Mediating ROS Production through Transcriptional Activation of Detoxification Genes
4.2. Mediating Oxidative Stress-Induced Cell Death via Ubiquitylation
4.3. Neuroprotection through Aggregate Accumulation, Clearance, and Degradation
5. NDD Regulation by ROS and the UPS: Moving Forward
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Schmidt-Sidor, B.; Mierzewska, H.; Turzyniecka, M.; Kowalewska-Kantecka, B.; Wierzba-Bobrowicz, T.; Lechowicz, W. Neurodegenerative disease in infants with multiple congenital malformations—Report of two cases. Folia Neuropathol. 2004, 42, 221–226. [Google Scholar] [PubMed]
- Silbereis, J.C.; Pochareddy, S.; Zhu, Y.; Li, M.; Sestan, N. The Cellular and Molecular Landscapes of the Developing Human Central Nervous System. Neuron 2016, 89, 248–268. [Google Scholar] [CrossRef] [PubMed]
- Thau, L.; Reddy, V.; Singh, P. Anatomy, Central Nervous System; StatPearls Publishing: Treasure Island, FL, USA, 2020. [Google Scholar]
- Sjodin, S.; Brinkmalm, G.; Ohrfelt, A.; Parnetti, L.; Paciotti, S.; Hansson, O.; Hardy, J.; Blennow, K.; Zetterberg, H.; Brinkmalm, A. Endo-lysosomal proteins and ubiquitin CSF concentrations in Alzheimer’s and Parkinson’s disease. Alzheimers Res. Ther. 2019, 11, 82. [Google Scholar] [CrossRef] [PubMed]
- Arnold, J.; Dawson, S.; Fergusson, J.; Lowe, J.; Landon, M.; Mayer, R.J. Ubiquitin and its role in neurodegeneration. Prog. Brain Res. 1998, 117, 23–34. [Google Scholar] [CrossRef] [PubMed]
- Huang, Q.; Figueiredo-Pereira, M.E. Ubiquitin/proteasome pathway impairment in neurodegeneration: Therapeutic implications. Apoptosis 2010, 15, 1292–1311. [Google Scholar] [CrossRef]
- Ghavami, S.; Shojaei, S.; Yeganeh, B.; Ande, S.R.; Jangamreddy, J.R.; Mehrpour, M.; Christoffersson, J.; Chaabane, W.; Moghadam, A.R.; Kashani, H.H.; et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog. Neurobiol. 2014, 112, 24–49. [Google Scholar] [CrossRef] [PubMed]
- Heemels, M.T. Neurodegenerative diseases. Nature 2016, 539, 179. [Google Scholar] [CrossRef]
- Kerr, J.S.; Adriaanse, B.A.; Greig, N.H.; Mattson, M.P.; Cader, M.Z.; Bohr, V.A.; Fang, E.F. Mitophagy and Alzheimer’s Disease: Cellular and Molecular Mechanisms. Trends Neurosci. 2017, 40, 151–166. [Google Scholar] [CrossRef]
- Ferreira-Vieira, T.H.; Guimaraes, I.M.; Silva, F.R.; Ribeiro, F.M. Alzheimer’s disease: Targeting the Cholinergic System. Curr. Neuropharmacol. 2016, 14, 101–115. [Google Scholar] [CrossRef]
- Wakabayashi, K.; Tanji, K.; Odagiri, S.; Miki, Y.; Mori, F.; Takahashi, H. The Lewy body in Parkinson’s disease and related neurodegenerative disorders. Mol. Neurobiol. 2013, 47, 495–508. [Google Scholar] [CrossRef]
- Kalia, L.V.; Lang, A.E. Parkinson’s disease. Lancet 2015, 386, 896–912. [Google Scholar] [CrossRef]
- Roze, E.; Cahill, E.; Martin, E.; Bonnet, C.; Vanhoutte, P.; Betuing, S.; Caboche, J. Huntington’s Disease and Striatal Signaling. Front. Neuroanat. 2011, 5, 55. [Google Scholar] [CrossRef]
- Lee, P.L.; Chou, K.H.; Chung, C.P.; Lai, T.H.; Zhou, J.H.; Wang, P.N.; Lin, C.P. Posterior Cingulate Cortex Network Predicts Alzheimer’s Disease Progression. Front. Aging Neurosci. 2020, 12, 608667. [Google Scholar] [CrossRef] [PubMed]
- Reiner, A.; Dragatsis, I.; Dietrich, P. Genetics and neuropathology of Huntington’s disease. Int. Rev. Neurobiol. 2011, 98, 325–372. [Google Scholar] [CrossRef]
- Pan, M.; Zheng, Q.; Yu, Y.; Ai, H.; Xie, Y.; Zeng, X.; Wang, C.; Liu, L.; Zhao, M. Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative. Nat. Commun. 2021, 12, 121. [Google Scholar] [CrossRef]
- Minagar, A.; Barnett, M.H.; Benedict, R.H.; Pelletier, D.; Pirko, I.; Sahraian, M.A.; Frohman, E.; Zivadinov, R. The thalamus and multiple sclerosis: Modern views on pathologic, imaging, and clinical aspects. Neurology 2013, 80, 210–219. [Google Scholar] [CrossRef]
- Liptak, Z.; Berger, A.M.; Sampat, M.P.; Charil, A.; Felsovalyi, O.; Healy, B.C.; Hildenbrand, P.; Khoury, S.J.; Weiner, H.L.; Bakshi, R.; et al. Medulla oblongata volume: A biomarker of spinal cord damage and disability in multiple sclerosis. AJNR Am. J. Neuroradiol. 2008, 29, 1465–1470. [Google Scholar] [CrossRef] [PubMed]
- Prakash, K.G.; Bannur, B.M.; Chavan, M.D.; Saniya, K.; Sailesh, K.S.; Rajagopalan, A. Neuroanatomical changes in Parkinson’s disease in relation to cognition: An update. J. Adv. Pharm. Technol. Res. 2016, 7, 123–126. [Google Scholar] [CrossRef] [PubMed]
- Vonsattel, J.P.; DiFiglia, M. Huntington disease. J. Neuropathol. Exp. Neurol. 1998, 57, 369–384. [Google Scholar] [CrossRef]
- Schaefer, M.H.; Wanker, E.E.; Andrade-Navarro, M.A. Evolution and function of CAG/polyglutamine repeats in protein-protein interaction networks. Nucleic Acids Res. 2012, 40, 4273–4287. [Google Scholar] [CrossRef]
- Dayalu, P.; Albin, R.L. Huntington disease: Pathogenesis and treatment. Neurol. Clin. 2015, 33, 101–114. [Google Scholar] [CrossRef]
- Frank, S. Treatment of Huntington’s disease. Neurotherapeutics 2014, 11, 153–160. [Google Scholar] [CrossRef]
- Lempriere, S. Huntington disease alters early neurodevelopment. Nat. Rev. Neurol. 2020, 16, 459. [Google Scholar] [CrossRef] [PubMed]
- Zheng, P.; Kozloski, J. Striatal Network Models of Huntington’s Disease Dysfunction Phenotypes. Front. Comput. Neurosci. 2017, 11, 70. [Google Scholar] [CrossRef]
- Graybiel, A.M. The basal ganglia and chunking of action repertoires. Neurobiol. Learn. Mem. 1998, 70, 119–136. [Google Scholar] [CrossRef]
- La Spada, A.R.; Paulson, H.L.; Fischbeck, K.H. Trinucleotide repeat expansion in neurological disease. Ann. Neurol. 1994, 36, 814–822. [Google Scholar] [CrossRef]
- Consortium, H.D.I. Developmental alterations in Huntington’s disease neural cells and pharmacological rescue in cells and mice. Nat. Neurosci. 2017, 20, 648–660. [Google Scholar] [CrossRef] [PubMed]
- Shirasaki, D.I.; Greiner, E.R.; Al-Ramahi, I.; Gray, M.; Boontheung, P.; Geschwind, D.H.; Botas, J.; Coppola, G.; Horvath, S.; Loo, J.A.; et al. Network organization of the huntingtin proteomic interactome in mammalian brain. Neuron 2012, 75, 41–57. [Google Scholar] [CrossRef] [PubMed]
- Singh, A.; Kukreti, R.; Saso, L.; Kukreti, S. Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules 2019, 24, 1583. [Google Scholar] [CrossRef] [PubMed]
- Angelova, P.R.; Abramov, A.Y. Role of mitochondrial ROS in the brain: From physiology to neurodegeneration. FEBS Lett. 2018, 592, 692–702. [Google Scholar] [CrossRef] [PubMed]
- Frost, J.L.; Schafer, D.P. Microglia: Architects of the Developing Nervous System. Trends Cell Biol. 2016, 26, 587–597. [Google Scholar] [CrossRef]
- Bachiller, S.; Jimenez-Ferrer, I.; Paulus, A.; Yang, Y.; Swanberg, M.; Deierborg, T.; Boza-Serrano, A. Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response. Front. Cell. Neurosci. 2018, 12, 488. [Google Scholar] [CrossRef]
- Jessen, K.R. Glial cells. Int. J. Biochem. Cell Biol. 2004, 36, 1861–1867. [Google Scholar] [CrossRef]
- Villa, V.; Thellung, S.; Bajetto, A.; Gatta, E.; Robello, M.; Novelli, F.; Tasso, B.; Tonelli, M.; Florio, T. Novel celecoxib analogues inhibit glial production of prostaglandin E2, nitric oxide, and oxygen radicals reverting the neuroinflammatory responses induced by misfolded prion protein fragment 90-231 or lipopolysaccharide. Pharmacol. Res. 2016, 113, 500–514. [Google Scholar] [CrossRef] [PubMed]
- Liddelow, S.A.; Guttenplan, K.A.; Clarke, L.E.; Bennett, F.C.; Bohlen, C.J.; Schirmer, L.; Bennett, M.L.; Munch, A.E.; Chung, W.S.; Peterson, T.C.; et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017, 541, 481–487. [Google Scholar] [CrossRef]
- Daneman, R.; Prat, A. The blood-brain barrier. Cold Spring Harb. Perspect. Biol. 2015, 7, a020412. [Google Scholar] [CrossRef] [PubMed]
- Sofroniew, M.V.; Vinters, H.V. Astrocytes: Biology and pathology. Acta Neuropathol. 2010, 119, 7–35. [Google Scholar] [CrossRef]
- Lecuyer, M.A.; Kebir, H.; Prat, A. Glial influences on BBB functions and molecular players in immune cell trafficking. Biochim. Biophys. Acta 2016, 1862, 472–482. [Google Scholar] [CrossRef]
- Persidsky, Y.; Ramirez, S.H.; Haorah, J.; Kanmogne, G.D. Blood-brain barrier: Structural components and function under physiologic and pathologic conditions. J. Neuroimmune Pharmacol. 2006, 1, 223–236. [Google Scholar] [CrossRef] [PubMed]
- Vrselja, Z.; Brkic, H.; Mrdenovic, S.; Radic, R.; Curic, G. Function of circle of Willis. J. Cereb. Blood Flow Metab. 2014, 34, 578–584. [Google Scholar] [CrossRef]
- Roher, A.E.; Esh, C.; Kokjohn, T.A.; Kalback, W.; Luehrs, D.C.; Seward, J.D.; Sue, L.I.; Beach, T.G. Circle of willis atherosclerosis is a risk factor for sporadic Alzheimer’s disease. Arterioscler. Thromb. Vasc. Biol. 2003, 23, 2055–2062. [Google Scholar] [CrossRef] [PubMed]
- Cai, Z.; Qiao, P.F.; Wan, C.Q.; Cai, M.; Zhou, N.K.; Li, Q. Role of Blood-Brain Barrier in Alzheimer’s Disease. J. Alzheimers Dis. 2018, 63, 1223–1234. [Google Scholar] [CrossRef] [PubMed]
- Harris, J.J.; Attwell, D. The energetics of CNS white matter. J. Neurosci. 2012, 32, 356–371. [Google Scholar] [CrossRef] [PubMed]
- Fernie, A.R.; Carrari, F.; Sweetlove, L.J. Respiratory metabolism: Glycolysis, the TCA cycle and mitochondrial electron transport. Curr. Opin. Plant Biol. 2004, 7, 254–261. [Google Scholar] [CrossRef] [PubMed]
- Dasuri, K.; Zhang, L.; Keller, J.N. Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis. Free Radic. Biol. Med. 2013, 62, 170–185. [Google Scholar] [CrossRef]
- Sbodio, J.I.; Snyder, S.H.; Paul, B.D. Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities. Antioxid. Redox Signal. 2019, 30, 1450–1499. [Google Scholar] [CrossRef] [PubMed]
- Ferrer-Sueta, G.; Manta, B.; Botti, H.; Radi, R.; Trujillo, M.; Denicola, A. Factors affecting protein thiol reactivity and specificity in peroxide reduction. Chem. Res. Toxicol. 2011, 24, 434–450. [Google Scholar] [CrossRef]
- Santos, A.L.; Lindner, A.B. Protein Posttranslational Modifications: Roles in Aging and Age-Related Disease. Oxid. Med. Cell. Longev. 2017, 2017, 5716409. [Google Scholar] [CrossRef]
- Duan, J.; Gaffrey, M.J.; Qian, W.J. Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines. Mol. Biosyst. 2017, 13, 816–829. [Google Scholar] [CrossRef]
- Shin, M.K.; Vazquez-Rosa, E.; Koh, Y.; Dhar, M.; Chaubey, K.; Cintron-Perez, C.J.; Barker, S.; Miller, E.; Franke, K.; Noterman, M.F.; et al. Reducing acetylated tau is neuroprotective in brain injury. Cell 2021, 184, 2715–2732. [Google Scholar] [CrossRef]
- Tracy, T.E.; Sohn, P.D.; Minami, S.S.; Wang, C.; Min, S.W.; Li, Y.; Zhou, Y.; Le, D.; Lo, I.; Ponnusamy, R.; et al. Acetylated Tau Obstructs KIBRA-Mediated Signaling in Synaptic Plasticity and Promotes Tauopathy-Related Memory Loss. Neuron 2016, 90, 245–260. [Google Scholar] [CrossRef] [PubMed]
- Snezhkina, A.V.; Kudryavtseva, A.V.; Kardymon, O.L.; Savvateeva, M.V.; Melnikova, N.V.; Krasnov, G.S.; Dmitriev, A.A. ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells. Oxid. Med. Cell. Longev. 2019, 2019, 6175804. [Google Scholar] [CrossRef] [PubMed]
- Di Meo, S.; Reed, T.T.; Venditti, P.; Victor, V.M. Role of ROS and RNS Sources in Physiological and Pathological Conditions. Oxid. Med. Cell. Longev. 2016, 2016, 1245049. [Google Scholar] [CrossRef] [PubMed]
- Weitzberg, E.; Hezel, M.; Lundberg, J.O. Nitrate-nitrite-nitric oxide pathway: Implications for anesthesiology and intensive care. Anesthesiology 2010, 113, 1460–1475. [Google Scholar] [CrossRef]
- Petushkova, A.I.; Zamyatnin, A.A., Jr. Redox-Mediated Post-Translational Modifications of Proteolytic Enzymes and Their Role in Protease Functioning. Biomolecules 2020, 10, 650. [Google Scholar] [CrossRef]
- Goyal, M.M.; Basak, A. Hydroxyl radical generation theory: A possible explanation of unexplained actions of mammalian catalase. Int. J. Biochem. Mol. Biol. 2012, 3, 282–289. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Chen, S.X.; Schopfer, P. Hydroxyl-radical production in physiological reactions. A novel function of peroxidase. Eur. J. Biochem. 1999, 260, 726–735. [Google Scholar] [CrossRef]
- Beckman, J.S.; Beckman, T.W.; Chen, J.; Marshall, P.A.; Freeman, B.A. Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. USA 1990, 87, 1620–1624. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Argiles-Castillo, D.; Kane, E.I.; Zhou, A.; Spratt, D.E. Correction: HECT E3 ubiquitin ligases—Emerging insights into their biological roles and disease relevance. J. Cell Sci. 2020, 133, jcs258087. [Google Scholar] [CrossRef]
- Metzger, M.B.; Pruneda, J.N.; Klevit, R.E.; Weissman, A.M. RING-type E3 ligases: Master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Biochim. Biophys. Acta 2014, 1843, 47–60. [Google Scholar] [CrossRef]
- Akutsu, M.; Dikic, I.; Bremm, A. Ubiquitin chain diversity at a glance. J. Cell Sci. 2016, 129, 875–880. [Google Scholar] [CrossRef]
- Komander, D.; Rape, M. The ubiquitin code. Annu. Rev. Biochem. 2012, 81, 203–229. [Google Scholar] [CrossRef]
- Swatek, K.N.; Komander, D. Ubiquitin modifications. Cell Res. 2016, 26, 399–422. [Google Scholar] [CrossRef]
- Hershko, A.; Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem. 1998, 67, 425–479. [Google Scholar] [CrossRef]
- Spratt, D.E.; Walden, H.; Shaw, G.S. RBR E3 ubiquitin ligases: New structures, new insights, new questions. Biochem. J. 2014, 458, 421–437. [Google Scholar] [CrossRef]
- Das, T.; Shin, S.C.; Song, E.J.; Kim, E.E. Regulation of Deubiquitinating Enzymes by Post-Translational Modifications. Int. J. Mol. Sci. 2020, 21, 4028. [Google Scholar] [CrossRef] [PubMed]
- Kriegenburg, F.; Poulsen, E.G.; Koch, A.; Kruger, E.; Hartmann-Petersen, R. Redox control of the ubiquitin-proteasome system: From molecular mechanisms to functional significance. Antioxid. Redox Signal. 2011, 15, 2265–2299. [Google Scholar] [CrossRef] [PubMed]
- Demasi, M.; Simoes, V.; Bonatto, D. Cross-talk between redox regulation and the ubiquitin-proteasome system in mammalian cell differentiation. Biochim. Biophys. Acta 2015, 1850, 1594–1606. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Jiang, X.; Feng, F.; Liu, W.; Sun, H. Degradation of proteins by PROTACs and other strategies. Acta Pharm. Sin. B 2020, 10, 207–238. [Google Scholar] [CrossRef] [PubMed]
- Schreiber, S.L. The Rise of Molecular Glues. Cell 2021, 184, 3–9. [Google Scholar] [CrossRef] [PubMed]
- Lim, K.H.; Joo, J.Y.; Baek, K.H. The potential roles of deubiquitinating enzymes in brain diseases. Ageing Res. Rev. 2020, 61, 101088. [Google Scholar] [CrossRef] [PubMed]
- Acevedo, A.; Gonzalez-Billault, C. Crosstalk between Rac1-mediated actin regulation and ROS production. Free Radic. Biol. Med. 2018, 116, 101–113. [Google Scholar] [CrossRef] [PubMed]
- Patil, S.; Bunderson, M.; Wilham, J.; Black, S.M. Important role for Rac1 in regulating reactive oxygen species generation and pulmonary arterial smooth muscle cell growth. Am. J. Physiol. Lung Cell. Mol. Physiol. 2004, 287, L1314–L1322. [Google Scholar] [CrossRef][Green Version]
- Ponten, F.; Jirstrom, K.; Uhlen, M. The Human Protein Atlas—A tool for pathology. J. Pathol. 2008, 216, 387–393. [Google Scholar] [CrossRef]
- Uhlen, M.; Oksvold, P.; Fagerberg, L.; Lundberg, E.; Jonasson, K.; Forsberg, M.; Zwahlen, M.; Kampf, C.; Wester, K.; Hober, S.; et al. Towards a knowledge-based Human Protein Atlas. Nat. Biotechnol. 2010, 28, 1248–1250. [Google Scholar] [CrossRef]
- Kikuchi, M.; Sekiya, M.; Hara, N.; Miyashita, A.; Kuwano, R.; Ikeuchi, T.; Iijima, K.M.; Nakaya, A. Disruption of a RAC1-centred network is associated with Alzheimer’s disease pathology and causes age-dependent neurodegeneration. Hum. Mol. Genet. 2020, 29, 817–833. [Google Scholar] [CrossRef]
- Chen, L.; Melendez, J.; Campbell, K.; Kuan, C.Y.; Zheng, Y. Rac1 deficiency in the forebrain results in neural progenitor reduction and microcephaly. Dev. Biol. 2009, 325, 162–170. [Google Scholar] [CrossRef]
- Deng, H.X. HACE1, RAC1, and what else in the pathogenesis of SPPRS? Neurol. Genet. 2019, 5, e326. [Google Scholar] [CrossRef] [PubMed]
- Reijnders, M.R.F.; Ansor, N.M.; Kousi, M.; Yue, W.W.; Tan, P.L.; Clarkson, K.; Clayton-Smith, J.; Corning, K.; Jones, J.R.; Lam, W.W.K.; et al. RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes. Am. J. Hum. Genet. 2017, 101, 466–477. [Google Scholar] [CrossRef]
- Tourette, C.; Li, B.; Bell, R.; O’Hare, S.; Kaltenbach, L.S.; Mooney, S.D.; Hughes, R.E. A large scale Huntingtin protein interaction network implicates Rho GTPase signaling pathways in Huntington disease. J. Biol. Chem. 2014, 289, 6709–6726. [Google Scholar] [CrossRef] [PubMed]
- Tousley, A.; Iuliano, M.; Weisman, E.; Sapp, E.; Zhang, N.; Vodicka, P.; Alexander, J.; Aviolat, H.; Gatune, L.; Reeves, P.; et al. Rac1 Activity Is Modulated by Huntingtin and Dysregulated in Models of Huntington’s Disease. J. Huntingtons Dis. 2019, 8, 53–69. [Google Scholar] [CrossRef]
- Zucchelli, S.; Codrich, M.; Marcuzzi, F.; Pinto, M.; Vilotti, S.; Biagioli, M.; Ferrer, I.; Gustincich, S. TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson’s disease brains. Hum. Mol. Genet. 2010, 19, 3759–3770. [Google Scholar] [CrossRef]
- Noguchi, T.; Takeda, K.; Matsuzawa, A.; Saegusa, K.; Nakano, H.; Gohda, J.; Inoue, J.; Ichijo, H. Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death. J. Biol. Chem. 2005, 280, 37033–37040. [Google Scholar] [CrossRef]
- Daugaard, M.; Nitsch, R.; Razaghi, B.; McDonald, L.; Jarrar, A.; Torrino, S.; Castillo-Lluva, S.; Rotblat, B.; Li, L.; Malliri, A.; et al. Hace1 controls ROS generation of vertebrate Rac1-dependent NADPH oxidase complexes. Nat. Commun. 2013, 4, 2180. [Google Scholar] [CrossRef]
- Mettouchi, A.; Lemichez, E. Ubiquitylation of active Rac1 by the E3 ubiquitin-ligase HACE1. Small GTPases 2012, 3, 102–106. [Google Scholar] [CrossRef] [PubMed]
- Ehrnhoefer, D.E.; Southwell, A.L.; Sivasubramanian, M.; Qiu, X.; Villanueva, E.B.; Xie, Y.; Waltl, S.; Anderson, L.; Fazeli, A.; Casal, L.; et al. HACE1 is essential for astrocyte mitochondrial function and influences Huntington disease phenotypes in vivo. Hum. Mol. Genet. 2018, 27, 239–253. [Google Scholar] [CrossRef] [PubMed]
- Zhang, P.; Wang, C.; Gao, K.; Wang, D.; Mao, J.; An, J.; Xu, C.; Wu, D.; Yu, H.; Liu, J.O.; et al. The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation. J. Biol. Chem. 2010, 285, 8869–8879. [Google Scholar] [CrossRef] [PubMed]
- Mund, T.; Masuda-Suzukake, M.; Goedert, M.; Pelham, H.R. Ubiquitination of alpha-synuclein filaments by Nedd4 ligases. PLoS ONE 2018, 13, e0200763. [Google Scholar] [CrossRef] [PubMed]
- Kwak, Y.D.; Wang, B.; Li, J.J.; Wang, R.; Deng, Q.; Diao, S.; Chen, Y.; Xu, R.; Masliah, E.; Xu, H.; et al. Upregulation of the E3 ligase NEDD4-1 by oxidative stress degrades IGF-1 receptor protein in neurodegeneration. J. Neurosci. 2012, 32, 10971–10981. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Kim, W.S.; Rahmanto, A.S.; Kamili, A.; Rye, K.A.; Guillemin, G.J.; Gelissen, I.C.; Jessup, W.; Hill, A.F.; Garner, B. Role of ABCG1 and ABCA1 in regulation of neuronal cholesterol efflux to apolipoprotein E discs and suppression of amyloid-beta peptide generation. J. Biol. Chem. 2007, 282, 2851–2861. [Google Scholar] [CrossRef] [PubMed]
- Oh, S.J.; Lee, C.J. Distribution and Function of the Bestrophin-1 (Best1) Channel in the Brain. Exp. Neurobiol. 2017, 26, 113–121. [Google Scholar] [CrossRef]
- Park, M.; Jung, H.G.; Kweon, H.J.; Kim, Y.E.; Park, J.Y.; Hwang, E.M. The E3 ubiquitin ligase, NEDD4L (NEDD4-2) regulates bestrophin-1 (BEST1) by ubiquitin-dependent proteolysis. Biochem. Biophys. Res. Commun. 2019, 514, 344–350. [Google Scholar] [CrossRef] [PubMed]
- Rott, R.; Szargel, R.; Haskin, J.; Bandopadhyay, R.; Lees, A.J.; Shani, V.; Engelender, S. alpha-Synuclein fate is determined by USP9X-regulated monoubiquitination. Proc. Natl. Acad. Sci. USA 2011, 108, 18666–18671. [Google Scholar] [CrossRef] [PubMed]
- Hara, M.R.; Agrawal, N.; Kim, S.F.; Cascio, M.B.; Fujimuro, M.; Ozeki, Y.; Takahashi, M.; Cheah, J.H.; Tankou, S.K.; Hester, L.D.; et al. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat. Cell Biol. 2005, 7, 665–674. [Google Scholar] [CrossRef]
- Nagano, Y.; Yamashita, H.; Takahashi, T.; Kishida, S.; Nakamura, T.; Iseki, E.; Hattori, N.; Mizuno, Y.; Kikuchi, A.; Matsumoto, M. Siah-1 facilitates ubiquitination and degradation of synphilin-1. J. Biol. Chem. 2003, 278, 51504–51514. [Google Scholar] [CrossRef]
- Kobayashi, A.; Kang, M.I.; Okawa, H.; Ohtsuji, M.; Zenke, Y.; Chiba, T.; Igarashi, K.; Yamamoto, M. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol. 2004, 24, 7130–7139. [Google Scholar] [CrossRef] [PubMed]
- Villeneuve, N.F.; Lau, A.; Zhang, D.D. Regulation of the Nrf2-Keap1 antioxidant response by the ubiquitin proteasome system: An insight into cullin-ring ubiquitin ligases. Antioxid. Redox Signal. 2010, 13, 1699–1712. [Google Scholar] [CrossRef]
- Gerez, J.A.; Prymaczok, N.C.; Rockenstein, E.; Herrmann, U.S.; Schwarz, P.; Adame, A.; Enchev, R.I.; Courtheoux, T.; Boersema, P.J.; Riek, R.; et al. A cullin-RING ubiquitin ligase targets exogenous alpha-synuclein and inhibits Lewy body-like pathology. Sci. Transl. Med. 2019, 11, eaau6722. [Google Scholar] [CrossRef] [PubMed]
- Seirafi, M.; Kozlov, G.; Gehring, K. Parkin structure and function. FEBS J. 2015, 282, 2076–2088. [Google Scholar] [CrossRef]
- Yoon, J.H.; Ann, E.J.; Kim, M.Y.; Ahn, J.S.; Jo, E.H.; Lee, H.J.; Lee, H.W.; Lee, Y.C.; Kim, J.S.; Park, H.S. Parkin mediates neuroprotection through activation of Notch1 signaling. Neuroreport 2017, 28, 181–186. [Google Scholar] [CrossRef] [PubMed]
- Acosta, M.I.; Urbach, S.; Doye, A.; Ng, Y.W.; Boudeau, J.; Mettouchi, A.; Debant, A.; Manser, E.; Visvikis, O.; Lemichez, E. Group-I PAKs-mediated phosphorylation of HACE1 at serine 385 regulates its oligomerization state and Rac1 ubiquitination. Sci. Rep. 2018, 8, 1410. [Google Scholar] [CrossRef]
- Razaghi, B.; Steele, S.L.; Prykhozhij, S.V.; Stoyek, M.R.; Hill, J.A.; Cooper, M.D.; McDonald, L.; Lin, W.; Daugaard, M.; Crapoulet, N.; et al. hace1 Influences zebrafish cardiac development via ROS-dependent mechanisms. Dev. Dyn. 2018, 247, 289–303. [Google Scholar] [CrossRef] [PubMed]
- Kogler, M.; Tortola, L.; Negri, G.L.; Leopoldi, A.; El-Naggar, A.M.; Mereiter, S.; Gomez-Diaz, C.; Nitsch, R.; Tortora, D.; Kavirayani, A.M.; et al. HACE1 Prevents Lung Carcinogenesis via Inhibition of RAC-Family GTPases. Cancer Res. 2020, 80, 3009–3022. [Google Scholar] [CrossRef]
- Andrio, E.; Lotte, R.; Hamaoui, D.; Cherfils, J.; Doye, A.; Daugaard, M.; Sorensen, P.H.; Bost, F.; Ruimy, R.; Mettouchi, A.; et al. Identification of cancer-associated missense mutations in hace1 that impair cell growth control and Rac1 ubiquitylation. Sci. Rep. 2017, 7, 44779. [Google Scholar] [CrossRef]
- Li, L.; Ismael, S.; Nasoohi, S.; Sakata, K.; Liao, F.F.; McDonald, M.P.; Ishrat, T. Thioredoxin-Interacting Protein (TXNIP) Associated NLRP3 Inflammasome Activation in Human Alzheimer’s Disease Brain. J. Alzheimers Dis. 2019, 68, 255–265. [Google Scholar] [CrossRef]
- Kim, I.; Shin, S.H.; Lee, J.E.; Park, J.W. Oxygen sensor FIH inhibits HACE1-dependent ubiquitination of Rac1 to enhance metastatic potential in breast cancer cells. Oncogene 2019, 38, 3651–3666. [Google Scholar] [CrossRef] [PubMed]
- Yu, C.; Xiao, J.H. The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging. Oxid. Med. Cell. Longev. 2021, 2021, 6635460. [Google Scholar] [CrossRef]
- Hill, S.; Harrison, J.S.; Lewis, S.M.; Kuhlman, B.; Kleiger, G. Mechanism of Lysine 48 Selectivity during Polyubiquitin Chain Formation by the Ube2R1/2 Ubiquitin-Conjugating Enzyme. Mol. Cell. Biol. 2016, 36, 1720–1732. [Google Scholar] [CrossRef] [PubMed]
- Canning, P.; Bullock, A.N. New strategies to inhibit KEAP1 and the Cul3-based E3 ubiquitin ligases. Biochem. Soc. Trans. 2014, 42, 103–107. [Google Scholar] [CrossRef] [PubMed]
- Dou, Y.; Tian, X.; Zhang, J.; Wang, Z.; Chen, G. Roles of TRAF6 in Central Nervous System. Curr. Neuropharmacol. 2018, 16, 1306–1313. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Xu, J.; Lazarovici, P.; Quirion, R.; Zheng, W. cAMP Response Element-Binding Protein (CREB): A Possible Signaling Molecule Link in the Pathophysiology of Schizophrenia. Front. Mol. Neurosci. 2018, 11, 255. [Google Scholar] [CrossRef] [PubMed]
- Okamoto, S.; Lipton, S.A. S-Nitrosylation in neurogenesis and neuronal development. Biochim. Biophys. Acta 2015, 1850, 1588–1593. [Google Scholar] [CrossRef] [PubMed]
- Shishido, T.; Nagano, Y.; Araki, M.; Kurashige, T.; Obayashi, H.; Nakamura, T.; Takahashi, T.; Matsumoto, M.; Maruyama, H. Synphilin-1 has neuroprotective effects on MPP(+)-induced Parkinson’s disease model cells by inhibiting ROS production and apoptosis. Neurosci. Lett. 2019, 690, 145–150. [Google Scholar] [CrossRef]
- Zhang, S.; Taghibiglou, C.; Girling, K.; Dong, Z.; Lin, S.Z.; Lee, W.; Shyu, W.C.; Wang, Y.T. Critical role of increased PTEN nuclear translocation in excitotoxic and ischemic neuronal injuries. J. Neurosci. 2013, 33, 7997–8008. [Google Scholar] [CrossRef]
- Trotman, L.C.; Wang, X.; Alimonti, A.; Chen, Z.; Teruya-Feldstein, J.; Yang, H.; Pavletich, N.P.; Carver, B.S.; Cordon-Cardo, C.; Erdjument-Bromage, H.; et al. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell 2007, 128, 141–156. [Google Scholar] [CrossRef] [PubMed]
- Huang, S.S.; Hsu, L.J.; Chang, N.S. Functional role of WW domain-containing proteins in tumor biology and diseases: Insight into the role in ubiquitin-proteasome system. FASEB Bioadv. 2020, 2, 234–253. [Google Scholar] [CrossRef]
- Maddika, S.; Kavela, S.; Rani, N.; Palicharla, V.R.; Pokorny, J.L.; Sarkaria, J.N.; Chen, J. WWP2 is an E3 ubiquitin ligase for PTEN. Nat. Cell Biol. 2011, 13, 728–733. [Google Scholar] [CrossRef]
- Clements, C.M.; McNally, R.S.; Conti, B.J.; Mak, T.W.; Ting, J.P. DJ-1, a cancer- and Parkinson’s disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2. Proc. Natl. Acad. Sci. USA 2006, 103, 15091–15096. [Google Scholar] [CrossRef]
- Xiong, H.; Wang, D.; Chen, L.; Choo, Y.S.; Ma, H.; Tang, C.; Xia, K.; Jiang, W.; Ronai, Z.; Zhuang, X.; et al. Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. J. Clin. Investig. 2009, 119, 650–660. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Li, L.; Chin, L.S. Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage. Hum. Mol. Genet. 2010, 19, 2395–2408. [Google Scholar] [CrossRef] [PubMed]
- Richarme, G.; Mihoub, M.; Dairou, J.; Bui, L.C.; Leger, T.; Lamouri, A. Parkinsonism-associated protein DJ-1/Park7 is a major protein deglycase that repairs methylglyoxal- and glyoxal-glycated cysteine, arginine, and lysine residues. J. Biol. Chem. 2015, 290, 1885–1897. [Google Scholar] [CrossRef]
- Kinumi, T.; Kimata, J.; Taira, T.; Ariga, H.; Niki, E. Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells. Biochem. Biophys. Res. Commun. 2004, 317, 722–728. [Google Scholar] [CrossRef]
- Bonifati, V.; Rizzu, P.; van Baren, M.J.; Schaap, O.; Breedveld, G.J.; Krieger, E.; Dekker, M.C.; Squitieri, F.; Ibanez, P.; Joosse, M.; et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 2003, 299, 256–259. [Google Scholar] [CrossRef]
- Ariga, H.; Takahashi-Niki, K.; Kato, I.; Maita, H.; Niki, T.; Iguchi-Ariga, S.M. Neuroprotective function of DJ-1 in Parkinson’s disease. Oxid. Med. Cell. Longev. 2013, 2013, 683920. [Google Scholar] [CrossRef]
- Shinbo, Y.; Niki, T.; Taira, T.; Ooe, H.; Takahashi-Niki, K.; Maita, C.; Seino, C.; Iguchi-Ariga, S.M.; Ariga, H. Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities. Cell Death Differ. 2006, 13, 96–108. [Google Scholar] [CrossRef]
- Vogiatzi, T.; Xilouri, M.; Vekrellis, K.; Stefanis, L. Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J. Biol. Chem. 2008, 283, 23542–23556. [Google Scholar] [CrossRef]
- Mouchantaf, R.; Azakir, B.A.; McPherson, P.S.; Millard, S.M.; Wood, S.A.; Angers, A. The ubiquitin ligase itch is auto-ubiquitylated in vivo and in vitro but is protected from degradation by interacting with the deubiquitylating enzyme FAM/USP9X. J. Biol. Chem. 2006, 281, 38738–38747. [Google Scholar] [CrossRef]
Domains and Residue Boundaries | Role in Ubiquitylation | Experimentally Identified Interactor(s) | Neuroprotective Role | Proteopathic Outcome |
---|---|---|---|---|
TRAF6 (Q9Y4K3) | ||||
RING (70–190) TRAF-1 (150–202) TRAF-2 (203–259) | RING E3 Ligase | DJ-1 [83] α-synuclein [83] ASK1 [84] | Redox homeostasis Aggregation clearance Protein trafficking | PD, AD |
HACE1 (Q8IYU2) | ||||
AR (62–257) HECT (574–909) | HECT E3 Ligase | Rac1 [85,86] Nrf2 [86] Htt [87] | Redox homeostasis | PD, ALS, HD |
ITCH (Q96J02) | ||||
C2 (1–115) WW1 (326–259) WW2 (358–391) WW3 (438–471) WW4 (478–511) HECT (569–903) | HECT E3 Ligase | TXNIP [88] | Redox homeostasis | AD |
NEDD4 (P46934) | ||||
C2 (10–160) WW1 (610–643) WW2 (767–800) WW3 (840–873) WW4 (892–925) HECT (984–1318) | HECT E3 Ligase | α-synuclein [89] IGF-1Rβ [90] ABCG1 [91] | Redox homeostasis | AD, PD |
NED4L (Q96PU5) | ||||
C2 (4–126) WW1 (193–226) WW2 (385–418) WW3 (497–530) WW4 (548–581) HECT (640–974) | HECT E3 Ligase | BEST1 [92,93] | Redox homeostasis (Ca2+/Cl− current balance) | AD |
Usp9x (Q93008) | ||||
USP (1557–1956) | DUB | α-synuclein [94] | Proper spine development Neuronal chemical signaling Aggregation clearance | ASD, AD, PD |
SIAH1 (Q8IUQ4) | ||||
RING (41–76) SIAH-type (93–153) | RING E3 Ligase | GAPDH [95] synphilin-1 [96] | Oxidative stress response | PD |
Cullin3 (Q13618) | ||||
KLHL18 interaction (2–41) | RING E3 Ligase | KEAP1 [97] Nrf2 [98] α-synuclein [99] | Oxidative stress response | AD, PD |
Parkin (Q60260) | ||||
RING0 (141–225) RING1 (238–293) IBR (313–377) RING2 418–449) | RBR E3 Ligase | PINK1 [100] Notch1 [101] | Oxidative stress response Aggregation clearance | PD |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kane, E.I.; Waters, K.L.; Spratt, D.E. Intersection of Redox Chemistry and Ubiquitylation: Post-Translational Modifications Required for Maintaining Cellular Homeostasis and Neuroprotection. Cells 2021, 10, 2121. https://doi.org/10.3390/cells10082121
Kane EI, Waters KL, Spratt DE. Intersection of Redox Chemistry and Ubiquitylation: Post-Translational Modifications Required for Maintaining Cellular Homeostasis and Neuroprotection. Cells. 2021; 10(8):2121. https://doi.org/10.3390/cells10082121
Chicago/Turabian StyleKane, Emma I., Kelly L. Waters, and Donald E. Spratt. 2021. "Intersection of Redox Chemistry and Ubiquitylation: Post-Translational Modifications Required for Maintaining Cellular Homeostasis and Neuroprotection" Cells 10, no. 8: 2121. https://doi.org/10.3390/cells10082121
APA StyleKane, E. I., Waters, K. L., & Spratt, D. E. (2021). Intersection of Redox Chemistry and Ubiquitylation: Post-Translational Modifications Required for Maintaining Cellular Homeostasis and Neuroprotection. Cells, 10(8), 2121. https://doi.org/10.3390/cells10082121