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Proteins Cross-talking with Nox Complexes: The Social Life of Noxes

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NADPH Oxidases Revisited: From Function to Structure

Abstract

Nox NADPH Oxidases exhibit a basic organization comprising a catalytic transmembrane subunit closely regulated by canonical regulatory subunits, discussed in other chapters of this book. However, many additional proteins regulate the expression, assembly, structure, activity and subcellular traffic of Nox subunits. As such, they gravitate around Nox complexes and physically associate with at least one among the regulatory or catalytic subunits. Given that such associated proteins, in turn, exert canonical effects distinct from Nox regulation, they connect Nox function to physiological cell programs, mediating cross-talk to and from Noxes. This chapter provides a systematic overview of proteins for which the physical interaction with Noxes has been validated by “wet-lab” experiments. Such proteins support both stimulatory or inhibitory effects towards several aspects of Nox regulation and can be roughly classified as: (a) kinase-related organizers; (b) general organizers; (c) chaperone-like organizers; (d) RhoGTPase and/or cytoskeleton-related organizers; (e) scaffold proteins. In addition, we provide an overview of the Nox interactome “in silico”, indicating that Noxes cross-talk with their environment preferentially via interactive protein hubs associated with their regulatory, rather than catalytic subunits. Characterizing the roles of Nox-associated proteins is essential to provide an integrative understanding of Noxes within multiple cellular physiological contexts.

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References

  1. Shiose A, Sumimoto H (2000) Arachidonic acid and phosphorylation synergistically induce a conformational change of p47phox to activate the phagocyte NADPH oxidase. J Biol Chem 275(18):13793–13801

    Article  CAS  PubMed  Google Scholar 

  2. de Mendez I, Homayounpour N, Leto TL (1997) Specificity of p47phox SH3 domain interactions in NADPH oxidase assembly and activation. Mol Cell Biol 17(4):2177–2185

    Article  PubMed  PubMed Central  Google Scholar 

  3. El-Benna J et al (2009) p47phox, the phagocyte NADPH oxidase/NOX2 organizer: structure, phosphorylation and implication in diseases. Exp Mol Med 41(4):217–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Meijles DN et al (2014) Molecular insights of p47phox phosphorylation dynamics in the regulation of NADPH oxidase activation and superoxide production. J Biol Chem 289(33):22759–22770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wientjes FB et al (2001) The NADPH oxidase components p47(phox) and p40(phox) bind to moesin through their PX domain. Biochem Biophys Res Commun 289(2):382–388

    Article  CAS  PubMed  Google Scholar 

  6. Zhan Y et al (2004) p47(phox) PX domain of NADPH oxidase targets cell membrane via moesin-mediated association with the actin cytoskeleton. J Cell Biochem 92(4):795–809

    Article  CAS  PubMed  Google Scholar 

  7. Fontayne A et al (2002) Phosphorylation of p47phox sites by PKC alpha, beta II, delta, and zeta: effect on binding to p22phox and on NADPH oxidase activation. Biochemistry 41(24):7743–7750

    Article  CAS  PubMed  Google Scholar 

  8. Kilpatrick LE et al (2010) Regulation of TNF-induced oxygen radical production in human neutrophils: role of delta-PKC. J Leukoc Biol 87(1):153–164

    Article  CAS  PubMed  Google Scholar 

  9. Martyn KD et al (2005) p21-activated kinase (Pak) regulates NADPH oxidase activation in human neutrophils. Blood 106(12):3962–3969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dang PM et al (2006) A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites. J Clin Invest 116(7):2033–2043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dewas C et al (2000) The mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway is involved in formyl-methionyl-leucyl-phenylalanine-induced p47phox phosphorylation in human neutrophils. J Immunol 165(9):5238–5244

    Article  CAS  PubMed  Google Scholar 

  12. Chen Q et al (2003) Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. J Immunol 170(10):5302–5308

    Article  CAS  PubMed  Google Scholar 

  13. Hoyal CR et al (2003) Modulation of p47PHOX activity by site-specific phosphorylation: Akt-dependent activation of the NADPH oxidase. Proc Natl Acad Sci U S A 100(9):5130–5135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. El Benna J et al (1996) Activation of p38 in stimulated human neutrophils: phosphorylation of the oxidase component p47phox by p38 and ERK but not by JNK. Arch Biochem Biophys 334(2):395–400

    Article  PubMed  Google Scholar 

  15. El Benna J et al (1996) Phosphorylation of the respiratory burst oxidase subunit p47phox as determined by two-dimensional phosphopeptide mapping. Phosphorylation by protein kinase C, protein kinase A, and a mitogen-activated protein kinase. J Biol Chem 271(11):6374–6378

    Article  PubMed  Google Scholar 

  16. Kramer IM et al (1988) The 47-kDa protein involved in the NADPH:O2 oxidoreductase activity of human neutrophils is phosphorylated by cyclic AMP-dependent protein kinase without induction of a respiratory burst. Biochim Biophys Acta 971(2):189–196

    CAS  PubMed  Google Scholar 

  17. Pacquelet S et al (2007) Cross-talk between IRAK-4 and the NADPH oxidase. Biochem J 403(3):451–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chowdhury AK et al (2005) Src-mediated tyrosine phosphorylation of p47phox in hyperoxia-induced activation of NADPH oxidase and generation of reactive oxygen species in lung endothelial cells. J Biol Chem 280(21):20700–20711

    Article  CAS  PubMed  Google Scholar 

  19. Lewis EM et al (2010) Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. J Biol Chem 285(5):2959–2967

    Article  CAS  PubMed  Google Scholar 

  20. Sigal N, Gorzalczany Y, Pick E (2003) Two pathways of activation of the superoxide-generating NADPH oxidase of phagocytes in vitro—distinctive effects of inhibitors. Inflammation 27(3):147–159

    Article  CAS  PubMed  Google Scholar 

  21. Kudlik G et al (2020) Advances in understanding TKS4 and TKS5: molecular scaffolds regulating cellular processes from podosome and invadopodium formation to differentiation and tissue homeostasis. Int J Mol Sci 21(21)

    Google Scholar 

  22. Buschman MD et al (2009) The novel adaptor protein Tks4 (SH3PXD2B) is required for functional podosome formation. Mol Biol Cell 20(5):1302–1311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Seals DF et al (2005) The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells. Cancer Cell 7(2):155–165

    Article  CAS  PubMed  Google Scholar 

  24. Abram CL et al (2003) The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells. J Biol Chem 278(19):16844–16851

    Article  CAS  PubMed  Google Scholar 

  25. Gianni D et al (2009) Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 (Nox1) activity. Sci Signal 2(88):ra54

    Article  PubMed  PubMed Central  Google Scholar 

  26. Gianni D, DerMardirossian C, Bokoch GM (2011) Direct interaction between Tks proteins and the N-terminal proline-rich region (PRR) of NoxA1 mediates Nox1-dependent ROS generation. Eur J Cell Biol 90(2-3):164–171

    Article  CAS  PubMed  Google Scholar 

  27. Kawahara T, Quinn MT, Lambeth JD (2007) Molecular evolution of the reactive oxygen-generating NADPH oxidase (Nox/Duox) family of enzymes. BMC Evol Biol 7:109

    Article  PubMed  PubMed Central  Google Scholar 

  28. Diaz B et al (2009) Tks5-dependent, nox-mediated generation of reactive oxygen species is necessary for invadopodia formation. Sci Signal 2(88):ra53

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sies H et al (2022) Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nat Rev Mol Cell Biol 23(7):499–515

    Article  CAS  PubMed  Google Scholar 

  30. Yazdanpanah B et al (2009) Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. Nature 460(7259):1159–1163

    Article  CAS  PubMed  Google Scholar 

  31. Schramm M et al (2014) Riboflavin (vitamin B2 ) deficiency impairs NADPH oxidase 2 (Nox2) priming and defense against Listeria monocytogenes. Eur J Immunol 44(3):728–741

    Article  CAS  PubMed  Google Scholar 

  32. Park KJ et al (2012) Death receptors 4 and 5 activate Nox1 NADPH oxidase through riboflavin kinase to induce reactive oxygen species-mediated apoptotic cell death. J Biol Chem 287(5):3313–3325

    Article  CAS  PubMed  Google Scholar 

  33. Hatahet F, Ruddock LW (2009) Protein disulfide isomerase: a critical evaluation of its function in disulfide bond formation. Antioxid Redox Signal 11(11):2807–2850

    Article  CAS  PubMed  Google Scholar 

  34. Kozlov G et al (2010) A structural overview of the PDI family of proteins. FEBS J 277(19):3924–3936

    Article  CAS  PubMed  Google Scholar 

  35. Pirneskoski A et al (2004) Molecular characterization of the principal substrate binding site of the ubiquitous folding catalyst protein disulfide isomerase. J Biol Chem 279(11):10374–10381

    Article  CAS  PubMed  Google Scholar 

  36. Tian G et al (2006) The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites. Cell 124(1):61–73

    Article  CAS  PubMed  Google Scholar 

  37. Laurindo FR, Pescatore LA, Fernandes DEC (2012) Protein disulfide isomerase in redox cell signaling and homeostasis. Free Radic Biol Med 52(9):1954–1969

    Article  CAS  PubMed  Google Scholar 

  38. Römer RA et al (2016) The flexibility and dynamics of protein disulfide isomerase. Proteins 84(12):1776–1785

    Article  PubMed  PubMed Central  Google Scholar 

  39. Okumura M et al (2019) Dynamic assembly of protein disulfide isomerase in catalysis of oxidative folding. Nat Chem Biol 15(5):499–509

    Article  CAS  PubMed  Google Scholar 

  40. Hudson DA, Gannon SA, Thorpe C (2015) Oxidative protein folding: from thiol-disulfide exchange reactions to the redox poise of the endoplasmic reticulum. Free Radic Biol Med 80:171–182

    Article  CAS  PubMed  Google Scholar 

  41. Tanaka LY, Oliveira PVS, Laurindo FRM (2020) Peri/epicellular thiol oxidoreductases as mediators of extracellular redox signaling. Antioxid Redox Signal 33(4):280–307

    Article  CAS  PubMed  Google Scholar 

  42. Araujo TLS et al (2017) Protein disulfide isomerase externalization in endothelial cells follows classical and unconventional routes. Free Radic Biol Med 103:199–208

    Article  CAS  PubMed  Google Scholar 

  43. Flaumenhaft R, Furie B (2016) Vascular thiol isomerases. Blood 128(7):893–901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang L, Yu J, Wang CC (2021) Protein disulfide isomerase is regulated in multiple ways: Consequences for conformation, activities, and pathophysiological functions. Bioessays 43(3):e2000147

    Article  PubMed  Google Scholar 

  45. Xu S, Sankar S, Neamati N (2014) Protein disulfide isomerase: a promising target for cancer therapy. Drug Discov Today 19(3):222–240

    Article  CAS  PubMed  Google Scholar 

  46. Xiong B et al (2020) Protein disulfide isomerase in cardiovascular disease. Exp Mol Med 52(3):390–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Laurindo FR et al (2008) Novel role of protein disulfide isomerase in the regulation of NADPH oxidase activity: pathophysiological implications in vascular diseases. Antioxid Redox Signal 10(6):1101–1113

    Article  CAS  PubMed  Google Scholar 

  48. Janiszewski M et al (2005) Regulation of NAD(P)H oxidase by associated protein disulfide isomerase in vascular smooth muscle cells. J Biol Chem 280(49):40813–40819

    Article  CAS  PubMed  Google Scholar 

  49. Pescatore LA et al (2012) Protein disulfide isomerase is required for platelet-derived growth factor-induced vascular smooth muscle cell migration, Nox1 NADPH oxidase expression, and RhoGTPase activation. J Biol Chem 287(35):29290–29300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Santos CX et al (2009) Protein disulfide isomerase (PDI) associates with NADPH oxidase and is required for phagocytosis of Leishmania chagasi promastigotes by macrophages. J Leukoc Biol 86(4):989–998

    Article  CAS  PubMed  Google Scholar 

  51. de A Paes AM et al (2011) Protein disulfide isomerase redox-dependent association with p47(phox): evidence for an organizer role in leukocyte NADPH oxidase activation. J Leukoc Biol 90(4):799–810

    Article  PubMed  Google Scholar 

  52. Cho J (2013) Protein disulfide isomerase in thrombosis and vascular inflammation. J Thromb Haemost 11(12):2084–2091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fernandes DC et al (2009) Protein disulfide isomerase overexpression in vascular smooth muscle cells induces spontaneous preemptive NADPH oxidase activation and Nox1 mRNA expression: effects of nitrosothiol exposure. Arch Biochem Biophys 484(2):197–204

    Article  CAS  PubMed  Google Scholar 

  54. Fernandes DC et al (2021) PDIA1 acts as master organizer of NOX1/NOX4 balance and phenotype response in vascular smooth muscle. Free Radic Biol Med 162:603–614

    Article  CAS  PubMed  Google Scholar 

  55. Gimenez M et al (2019) Redox activation of Nox1 (NADPH oxidase 1) involves an intermolecular disulfide bond between protein disulfide isomerase and p47. Arterioscler Thromb Vasc Biol 39(2):224–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tanaka LY et al (2019) Peri/epicellular protein disulfide isomerase-A1 acts as an upstream organizer of cytoskeletal mechanoadaptation in vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 316(3):H566–H579

    Article  CAS  PubMed  Google Scholar 

  57. Soares Moretti AI, Martins Laurindo FR (2017) Protein disulfide isomerases: Redox connections in and out of the endoplasmic reticulum. Arch Biochem Biophys 617:106–119

    Article  CAS  PubMed  Google Scholar 

  58. Moretti AIS et al (2017) Conserved gene microsynteny unveils functional interaction between protein disulfide isomerase and Rho guanine-dissociation inhibitor families. Sci Rep 7(1):17262

    Article  PubMed  PubMed Central  Google Scholar 

  59. De Bessa TC et al (2019) Subverted regulation of Nox1 NADPH oxidase-dependent oxidant generation by protein disulfide isomerase A1 in colon carcinoma cells with overactivated KRas. Cell Death Dis 10(2):143

    Article  PubMed  PubMed Central  Google Scholar 

  60. Bechor E et al (2015) The dehydrogenase region of the NADPH oxidase component Nox2 acts as a protein disulfide isomerase (PDI) resembling PDIA3 with a role in the binding of the activator protein p67 (phox.). Front Chem 3:3

    Article  PubMed  PubMed Central  Google Scholar 

  61. Tanaka LY et al (2016) Peri/epicellular protein disulfide isomerase sustains vascular lumen caliber through an anticonstrictive remodeling effect. Hypertension 67(3):613–622

    Article  CAS  PubMed  Google Scholar 

  62. Brandes RP, Weissmann N, Schröder K (2014) Nox family NADPH oxidases in mechano-transduction: mechanisms and consequences. Antioxid Redox Signal 20(6):887–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sobierajska K et al (2014) Protein disulfide isomerase directly interacts with β-actin Cys374 and regulates cytoskeleton reorganization. J Biol Chem 289(9):5758–5773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Hsiai TK et al (2007) Hemodynamics influences vascular peroxynitrite formation: Implication for low-density lipoprotein apo-B-100 nitration. Free Radic Biol Med 42(4):519–529

    Article  CAS  PubMed  Google Scholar 

  65. Marschall R, Tudzynski P (2017) The protein disulfide isomerase of. Front Microbiol 8:960

    Article  PubMed  PubMed Central  Google Scholar 

  66. Laurindo FR, Araujo TL, Abrahão TB (2014) Nox NADPH oxidases and the endoplasmic reticulum. Antioxid Redox Signal 20(17):2755–2775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Prior KK et al (2016) The endoplasmic reticulum chaperone calnexin is a NADPH oxidase NOX4 interacting protein. J Biol Chem 291(13):7045–7059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zhang X et al (2019) Redox signals at the ER-mitochondria interface control melanoma progression. EMBO J 38(15):e100871

    Article  PubMed  PubMed Central  Google Scholar 

  69. George G et al (2020) EDEM2 stably disulfide-bonded to TXNDC11 catalyzes the first mannose trimming step in mammalian glycoprotein ERAD. Elife 9

    Google Scholar 

  70. Wang D et al (2005) Identification of a novel partner of duox: EFP1, a thioredoxin-related protein. J Biol Chem 280(4):3096–3103

    Article  CAS  PubMed  Google Scholar 

  71. De Deken X et al (2002) Characterization of ThOX proteins as components of the thyroid H(2)O(2)-generating system. Exp Cell Res 273(2):187–196

    Article  PubMed  Google Scholar 

  72. Arevalo JA, Vázquez-Medina JP (2018) The role of peroxiredoxin 6 in cell signaling. Antioxidants (Basel) 7(12)

    Google Scholar 

  73. Kwon J et al (2016) Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration. Free Radic Biol Med 96:99–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Krishnaiah SY et al (2013) p67(phox) terminates the phospholipase A(2)-derived signal for activation of NADPH oxidase (NOX2). FASEB J 27(5):2066–2073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Chatterjee S et al (2011) Peroxiredoxin 6 phosphorylation and subsequent phospholipase A2 activity are required for agonist-mediated activation of NADPH oxidase in mouse pulmonary microvascular endothelium and alveolar macrophages. J Biol Chem 286(13):11696–11706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hasegawa J et al (2011) SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain. J Cell Biol 193(5):901–916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kobayashi M et al (2014) Dock4 forms a complex with SH3YL1 and regulates cancer cell migration. Cell Signal 26(5):1082–1088

    Article  CAS  PubMed  Google Scholar 

  78. Yoo JY et al (2020) LPS-induced acute kidney injury is mediated by Nox4-SH3YL1. Cell Rep 33(3):108245

    Article  CAS  PubMed  Google Scholar 

  79. Nguyen MV et al (2013) Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4. Biochem Pharmacol 85(11):1644–1654

    Article  CAS  PubMed  Google Scholar 

  80. Yuan S et al (2021) Cooperation between CYB5R3 and NOX4 via coenzyme Q mitigates endothelial inflammation. Redox Biol 47:102166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ramadass M, Catz SD (2016) Molecular mechanisms regulating secretory organelles and endosomes in neutrophils and their implications for inflammation. Immunol Rev 273(1):249–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. McAdara Berkowitz JK et al (2001) JFC1, a novel tandem C2 domain-containing protein associated with the leukocyte NADPH oxidase. J Biol Chem 276(22):18855–18862

    Article  CAS  PubMed  Google Scholar 

  83. Munafó DB et al (2007) Rab27a is a key component of the secretory machinery of azurophilic granules in granulocytes. Biochem J 402(2):229–239

    Article  PubMed  PubMed Central  Google Scholar 

  84. Ramadass M et al (2019) The trafficking protein JFC1 regulates Rac1-GTP localization at the uropod controlling neutrophil chemotaxis and in vivo migration. J Leukoc Biol 105(6):1209–1224

    Article  CAS  PubMed  Google Scholar 

  85. Catz SD (2008) Characterization of Rab27a and JFC1 as constituents of the secretory machinery of prostate-specific antigen in prostate carcinoma cells. Methods Enzymol 438:25–40

    Article  CAS  PubMed  Google Scholar 

  86. Johnson JL et al (2010) Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms. Traffic 11(4):533–547

    Article  CAS  PubMed  Google Scholar 

  87. Ejlerskov P et al (2012) NADPH oxidase is internalized by clathrin-coated pits and localizes to a Rab27A/B GTPase-regulated secretory compartment in activated macrophages. J Biol Chem 287(7):4835–4852

    Article  CAS  PubMed  Google Scholar 

  88. Johnson JL et al (2016) Identification of neutrophil exocytosis inhibitors (nexinhibs), small molecule inhibitors of neutrophil exocytosis and inflammation: druggability of the small GTPase Rab27a. J Biol Chem 291(50):25965–25982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Johnson JL et al (2012) Vesicular trafficking through cortical actin during exocytosis is regulated by the Rab27a effector JFC1/Slp1 and the RhoA-GTPase-activating protein Gem-interacting protein. Mol Biol Cell 23(10):1902–1916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Thomas DC et al (2017) Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity. J Exp Med 214(4):1111–1128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Thomas DC et al (2019) EROS/CYBC1 mutations: decreased NADPH oxidase function and chronic granulomatous disease. J Allergy Clin Immunol 143(2):782–785.e1

    Article  CAS  PubMed  Google Scholar 

  92. Roos D et al (2021) Hematologically important mutations: X-linked chronic granulomatous disease (fourth update). Blood Cells Mol Dis 90:102587

    Article  CAS  PubMed  Google Scholar 

  93. Arnadottir GA et al (2018) A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease. Nat Commun 9(1):4447

    Article  PubMed  PubMed Central  Google Scholar 

  94. Perez-Heras I et al (2021) HSCT in two brothers with CGD arising from mutations in CYBC1 corrects the defect in neutrophil function. Clin Immunol 229:108799

    Article  CAS  PubMed  Google Scholar 

  95. Ryoden Y et al (2020) Functional expression of the P2X7 ATP receptor requires Eros. J Immunol 204(3):559–568

    Article  CAS  PubMed  Google Scholar 

  96. Boudreau E et al (1997) The chloroplast ycf3 and ycf4 open reading frames of Chlamydomonas reinhardtii are required for the accumulation of the photosystem I complex. EMBO J 16(20):6095–6104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Chen F et al (2011) Hsp90 regulates NADPH oxidase activity and is necessary for superoxide but not hydrogen peroxide production. Antioxid Redox Signal 14(11):2107–2119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Chen F et al (2015) Nox5 stability and superoxide production is regulated by C-terminal binding of Hsp90 and CO-chaperones. Free Radic Biol Med 89:793–805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Chen F et al (2012) Opposing actions of heat shock protein 90 and 70 regulate nicotinamide adenine dinucleotide phosphate oxidase stability and reactive oxygen species production. Arterioscler Thromb Vasc Biol 32(12):2989–2999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ahmad Mokhtar AMB et al (2021) A complete survey of RhoGDI targets reveals novel interactions with atypical small GTPases. Biochemistry 60(19):1533–1551

    Article  CAS  PubMed  Google Scholar 

  101. Pick E (2014) Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase: outsourcing a key task. Small GTPases 5:e27952

    Article  PubMed  PubMed Central  Google Scholar 

  102. Hordijk PL (2006) Regulation of NADPH oxidases: the role of Rac proteins. Circ Res 98(4):453–462

    Article  CAS  PubMed  Google Scholar 

  103. Garcia-Mata R, Boulter E, Burridge K (2011) The ‘invisible hand’: regulation of RHO GTPases by RHOGDIs. Nat Rev Mol Cell Biol 12(8):493–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. DerMardirossian C, Schnelzer A, Bokoch GM (2004) Phosphorylation of RhoGDI by Pak1 mediates dissociation of Rac GTPase. Mol Cell 15(1):117–127

    Article  CAS  PubMed  Google Scholar 

  105. Zhang B et al (2001) Oligomerization of Rac1 gtpase mediated by the carboxyl-terminal polybasic domain. J Biol Chem 276(12):8958–8967

    Article  CAS  PubMed  Google Scholar 

  106. Carol RJ et al (2005) A RhoGDP dissociation inhibitor spatially regulates growth in root hair cells. Nature 438(7070):1013–1016

    Article  CAS  PubMed  Google Scholar 

  107. Kreck ML et al (1996) Membrane association of Rac is required for high activity of the respiratory burst oxidase. Biochemistry 35(49):15683–15692

    Article  CAS  PubMed  Google Scholar 

  108. Gorzalczany Y et al (2000) Targeting of Rac1 to the phagocyte membrane is sufficient for the induction of NADPH oxidase assembly. J Biol Chem 275(51):40073–40081

    Article  CAS  PubMed  Google Scholar 

  109. Ugolev Y et al (2006) Liposomes comprising anionic but not neutral phospholipids cause dissociation of Rac(1 or 2) x RhoGDI complexes and support amphiphile-independent NADPH oxidase activation by such complexes. J Biol Chem 281(28):19204–19219

    Article  CAS  PubMed  Google Scholar 

  110. Ugolev Y et al (2008) Dissociation of Rac1(GDP).RhoGDI complexes by the cooperative action of anionic liposomes containing phosphatidylinositol 3,4,5-trisphosphate, Rac guanine nucleotide exchange factor, and GTP. J Biol Chem 283(32):22257–22271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Grizot S et al (2001) Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation. Biochemistry 40(34):10007–10013

    Article  CAS  PubMed  Google Scholar 

  112. Schaefer A, Reinhard NR, Hordijk PL (2014) Toward understanding RhoGTPase specificity: structure, function and local activation. Small GTPases 5(2):6

    Article  PubMed  Google Scholar 

  113. Price MO et al (2002) Rac activation induces NADPH oxidase activity in transgenic COSphox cells, and the level of superoxide production is exchange factor-dependent. J Biol Chem 277(21):19220–19228

    Article  CAS  PubMed  Google Scholar 

  114. Utomo A et al (2006) Vav proteins in neutrophils are required for FcgammaR-mediated signaling to Rac GTPases and nicotinamide adenine dinucleotide phosphate oxidase component p40(phox). J Immunol 177(9):6388–6397

    Article  CAS  PubMed  Google Scholar 

  115. Liu Y et al (2013) A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress. J Cell Biol 201(6):863–873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Mizrahi A et al (2005) Activation of the phagocyte NADPH oxidase by Rac Guanine nucleotide exchange factors in conjunction with ATP and nucleoside diphosphate kinase. J Biol Chem 280(5):3802–3811

    Article  CAS  PubMed  Google Scholar 

  117. Park HS et al (2004) Sequential activation of phosphatidylinositol 3-kinase, beta Pix, Rac1, and Nox1 in growth factor-induced production of H2O2. Mol Cell Biol 24(10):4384–4394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Kaito Y et al (2014) Nox1 activation by βPix and the role of Ser-340 phosphorylation. FEBS Lett 588(11):1997–2002

    Article  CAS  PubMed  Google Scholar 

  119. Bretscher A et al (2000) ERM-Merlin and EBP50 protein families in plasma membrane organization and function. Annu Rev Cell Dev Biol 16:113–143

    Article  CAS  PubMed  Google Scholar 

  120. Al Ghouleh I et al (2016) Binding of EBP50 to Nox organizing subunit p47phox is pivotal to cellular reactive species generation and altered vascular phenotype. Proc Natl Acad Sci U S A 113(36):E5308–E5317

    Article  PubMed  PubMed Central  Google Scholar 

  121. Weissbach L et al (1994) Identification of a human rasGAP-related protein containing calmodulin-binding motifs. J Biol Chem 269(32):20517–20521

    Article  CAS  PubMed  Google Scholar 

  122. Bashour AM et al (1997) IQGAP1, a Rac- and Cdc42-binding protein, directly binds and cross-links microfilaments. J Cell Biol 137(7):1555–1566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Ikeda S et al (2005) IQGAP1 regulates reactive oxygen species-dependent endothelial cell migration through interacting with Nox2. Arterioscler Thromb Vasc Biol 25(11):2295–2300

    Article  CAS  PubMed  Google Scholar 

  124. Hernandes MS, Lassègue B, Griendling KK (2017) Polymerase δ-interacting protein 2: a multifunctional protein. J Cardiovasc Pharmacol 69(6):335–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Lyle AN et al (2009) Poldip2, a novel regulator of Nox4 and cytoskeletal integrity in vascular smooth muscle cells. Circ Res 105(3):249–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Datla SR et al (2014) Poldip2 controls vascular smooth muscle cell migration by regulating focal adhesion turnover and force polarization. Am J Physiol Heart Circ Physiol 307(7):H945–H957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Vukelic S et al (2018) NOX4 (NADPH oxidase 4) and Poldip2 (polymerase δ-interacting protein 2) induce filamentous actin oxidation and promote its interaction with vinculin during integrin-mediated cell adhesion. Arterioscler Thromb Vasc Biol 38(10):2423–2434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Huff LP et al (2019) Polymerase-δ-interacting protein 2 activates the RhoGEF epithelial cell transforming sequence 2 in vascular smooth muscle cells. Am J Physiol Cell Physiol 316(5):C621–C631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Sutliff RL et al (2013) Polymerase delta interacting protein 2 sustains vascular structure and function. Arterioscler Thromb Vasc Biol 33(9):2154–2161

    Article  CAS  PubMed  Google Scholar 

  130. Datla SR et al (2019) Poldip2 knockdown inhibits vascular smooth muscle proliferation and neointima formation by regulating the expression of PCNA and p21. Lab Invest 99(3):387–398

    Article  CAS  PubMed  Google Scholar 

  131. Paredes F et al (2020) Mitochondrial protein Poldip2 (polymerase delta interacting protein 2) controls vascular smooth muscle differentiated phenotype by O-linked GlcNAc (N-acetylglucosamine) transferase-dependent inhibition of a ubiquitin proteasome system. Circ Res 126(1):41–56

    Article  CAS  PubMed  Google Scholar 

  132. Paredes F et al (2018) Poldip2 is an oxygen-sensitive protein that controls PDH and αKGDH lipoylation and activation to support metabolic adaptation in hypoxia and cancer. Proc Natl Acad Sci U S A 115(8):1789–1794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Hernandes MS et al (2018) Polymerase delta-interacting protein 2 deficiency protects against blood-brain barrier permeability in the ischemic brain. J Neuroinflamm 15(1):45

    Article  Google Scholar 

  134. Forrester SJ et al (2019) Poldip2 deficiency protects against lung edema and vascular inflammation in a model of acute respiratory distress syndrome. Clin Sci (Lond) 133(2):321–334

    Article  CAS  PubMed  Google Scholar 

  135. Nicolae CM et al (2014) The ADP-ribosyltransferase PARP10/ARTD10 interacts with proliferating cell nuclear antigen (PCNA) and is required for DNA damage tolerance. J Biol Chem 289(19):13627–13637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Warbrick E (1998) PCNA binding through a conserved motif. Bioessays 20(3):195–199

    Article  CAS  PubMed  Google Scholar 

  137. Witko-Sarsat V et al (2010) Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival. J Exp Med 207(12):2631–2645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Ohayon D et al (2016) Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia. Sci Rep 6:35561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Ohayon D et al (2019) Cytosolic PCNA interacts with p47phox and controls NADPH oxidase NOX2 activation in neutrophils. J Exp Med 216(11):2669–2687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Krummrei U et al (1995) Cyclophilin-A is a zinc-dependent DNA binding protein in macrophages. FEBS Lett 371(1):47–51

    Article  CAS  PubMed  Google Scholar 

  141. Nigro P, Pompilio G, Capogrossi MC (2013) Cyclophilin A: a key player for human disease. Cell Death Dis 4:e888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Jin ZG et al (2000) Cyclophilin A is a secreted growth factor induced by oxidative stress. Circ Res 87(9):789–796

    Article  CAS  PubMed  Google Scholar 

  143. Satoh K et al (2009) Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms. Nat Med 15(6):649–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Satoh K et al (2011) Cyclophilin A promotes cardiac hypertrophy in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 31(5):1116–1123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Soe NN et al (2013) Cyclophilin A is required for angiotensin II-induced p47phox translocation to caveolae in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 33(9):2147–2153

    Article  CAS  PubMed  Google Scholar 

  146. Dos Santos GP et al (2021) Cyclophilin 19 secreted in the host cell cytosol by Trypanosoma cruzi promotes ROS production required for parasite growth. Cell Microbiol 23(4):e13295

    CAS  PubMed  Google Scholar 

  147. Boussetta T et al (2010) The prolyl isomerase Pin1 acts as a novel molecular switch for TNF-alpha-induced priming of the NADPH oxidase in human neutrophils. Blood 116(26):5795–5802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Makni-Maalej K et al (2012) The TLR7/8 agonist CL097 primes N-formyl-methionyl-leucyl-phenylalanine-stimulated NADPH oxidase activation in human neutrophils: critical role of p47phox phosphorylation and the proline isomerase Pin1. J Immunol 189(9):4657–4665

    Article  CAS  PubMed  Google Scholar 

  149. Litchfield DW (2003) Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J 369(Pt 1):1–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Park HS et al (2001) Phosphorylation of the leucocyte NADPH oxidase subunit p47(phox) by casein kinase 2: conformation-dependent phosphorylation and modulation of oxidase activity. Biochem J 358(Pt 3):783–790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Kil IS et al (2015) S-Nitrosylation of p47(phox) enhances phosphorylation by casein kinase 2. Redox Rep 20(5):228–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Kim GS et al (2009) CK2 is a novel negative regulator of NADPH oxidase and a neuroprotectant in mice after cerebral ischemia. J Neurosci 29(47):14779–14789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Liu J et al (2013) Identification and characterization of a unique leucine-rich repeat protein (LRRC33) that inhibits Toll-like receptor-mediated NF-κB activation. Biochem Biophys Res Commun 434(1):28–34

    Article  CAS  PubMed  Google Scholar 

  154. Noubade R et al (2014) NRROS negatively regulates reactive oxygen species during host defence and autoimmunity. Nature 509(7499):235–239

    Article  CAS  PubMed  Google Scholar 

  155. Wong K et al (2017) Mice deficient in NRROS show abnormal microglial development and neurological disorders. Nat Immunol 18(6):633–641

    Article  CAS  PubMed  Google Scholar 

  156. Ma W et al (2019) LRRC33 is a novel binding and potential regulating protein of TGF-β1 function in human acute myeloid leukemia cells. PLoS One 14(10):e0213482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Anglesio MS et al (2004) Differential expression of a novel ankyrin containing E3 ubiquitin-protein ligase, Hace1, in sporadic Wilms’ tumor versus normal kidney. Hum Mol Genet 13(18):2061–2074

    Article  CAS  PubMed  Google Scholar 

  158. Daugaard M et al (2013) Hace1 controls ROS generation of vertebrate Rac1-dependent NADPH oxidase complexes. Nat Commun 4:2180

    Article  PubMed  Google Scholar 

  159. Torrino S et al (2011) The E3 ubiquitin-ligase HACE1 catalyzes the ubiquitylation of active Rac1. Dev Cell 21(5):959–965

    Article  CAS  PubMed  Google Scholar 

  160. Diebold BA et al (2004) Antagonistic cross-talk between Rac and Cdc42 GTPases regulates generation of reactive oxygen species. J Biol Chem 279(27):28136–28142

    Article  CAS  PubMed  Google Scholar 

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de Bessa, T.C., Laurindo, F.R.M. (2023). Proteins Cross-talking with Nox Complexes: The Social Life of Noxes. In: Pick, E. (eds) NADPH Oxidases Revisited: From Function to Structure. Springer, Cham. https://doi.org/10.1007/978-3-031-23752-2_22

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