The iron chaperone poly(rC)-binding protein 2 forms a metabolon with the heme oxygenase 1/cytochrome P450 reductase complex for heme catabolism and iron transfer

Journal of Biological Chemistry

Volumn 292, Issue 32, 2017, Pages 13205-13229

  Yanatori, Izumi ^a   Richardson, Des R ^b   Toyokuni, Shinya ^b,c   Kishi, Fumio ^a  

^a KAWASAKI MEDICAL SCHOOL   (Japan)

^b UNIVERSITY OF SYDNEY   (Australia)

^c NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON MONOXIDE; MAMMALS; METABOLISM; PORPHYRINS; RECOMBINANT PROTEINS;

BINDING PROTEINS; COMPLEX FORMATIONS; DELETION MUTANTS; DIVALENT METAL TRANSPORTERS; HEME OXYGENASE-1; HEME OXYGENASES; INTRACELLULAR IRON; NADPH-CYTOCHROME P450 REDUCTASE;

IRON;

CHAPERONE; CYTOCHROME P450 REDUCTASE; FERROUS ION; HEME OXYGENASE 1; IRON BINDING PROTEIN; IRON CHAPERONE POLY(RC) BINDING PROTEIN 2; MULTIENZYME COMPLEX; NUCLEIC ACID BINDING PROTEIN; POLY(RC) BINDING PROTEIN 3; POLY(RC) BINDING PROTEIN 4; UNCLASSIFIED DRUG; DMRT1 PROTEIN; HEME; HEME OXYGENASE; HEME OXYGENASE-2; HMOX1 PROTEIN, HUMAN; HYBRID PROTEIN; IRON; METALLOPORPHYRIN; PCBP2 PROTEIN, HUMAN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE FERRIHEMOPROTEIN REDUCTASE; RNA BINDING PROTEIN; STANNSOPORFIN; TRANSCRIPTION FACTOR;

ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; GENE DELETION; HUMAN; HUMAN CELL; IN VITRO STUDY; IRON TRANSPORT; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; PROTEIN PURIFICATION; SEQUENCE HOMOLOGY; AMINO ACID SUBSTITUTION; ANTAGONISTS AND INHIBITORS; BINDING COMPETITION; BINDING SITE; CELL LINE; CHEMISTRY; COMPARATIVE STUDY; GENETICS; METABOLISM; MUTATION; PROTEIN MULTIMERIZATION; PROTEIN TRANSPORT; RNA INTERFERENCE; STRUCTURAL HOMOLOGY; TRANSPORT AT THE CELLULAR LEVEL;

AMINO ACID SUBSTITUTION; BINDING SITES; BINDING, COMPETITIVE; BIOLOGICAL TRANSPORT; CELL LINE; GENE DELETION; HEME; HEME OXYGENASE (DECYCLIZING); HEME OXYGENASE-1; HUMANS; IRON; METALLOPORPHYRINS; MUTATION; NADPH-FERRIHEMOPROTEIN REDUCTASE; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN MULTIMERIZATION; PROTEIN TRANSPORT; RECOMBINANT FUSION PROTEINS; RNA INTERFERENCE; RNA-BINDING PROTEINS; STRUCTURAL HOMOLOGY, PROTEIN; TRANSCRIPTION FACTORS;

EID: 85027407766     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M117.776021     Document Type: Article

References (100)

1. Richardson, D. R., Lane, D. J., Becker, E. M., Huang, M. L., Whitnall, M., Suryo Rahmanto, Y., Sheftel, A. D., and Ponka, P. (2010) Mitochondrial iron trafficking and the integration of iron metabolism between the mi-tochondrion and cytosol. Proc. Natl. Acad. Sci. U.S.A. 107, 10775–10782
2. Dunn, L. L., Suryo Rahmanto, Y., and Richardson, D. R. (2007) Iron uptake and metabolism in the new millennium. Trends Cell Biol. 17, 93–100
3. Toyokuni, S. (1996) Iron-induced carcinogenesis: the role of redox regulation. Free Radic. Biol. Med. 20, 553–566
4. Finch, C. A. (1959) Body iron exchange in man. J. Clin. Invest. 38, 392–396
5. Green, R., Charlton, R., Seftel, H., Bothwell, T., Mayet, F., Adams, B., Finch, C., and Layrisse, M. (1968) Body iron excretion in man: a collaborative study. Am. J. Med. 45, 336 –353
6. Ponka, P., Beaumont, C., and Richardson, D. R. (1998) Function and regulation of transferrin and ferritin. Semin. Hematol. 35, 35–54
7. Hurrell, R., and Egli, I. (2010) Iron bioavailability and dietary reference values. Am. J. Clin. Nutr. 91, 1461S-1467S*
8. Kalinowski, D. S., Stefani, C., Toyokuni, S., Ganz, T., Anderson, G. J., Subramaniam, N. V., Trinder, D., Olynyk, J. K., Chua, A., Jansson, P. J., Sahni, S., Lane, D. J., Merlot, A. M., Kovacevic, Z., Huang, M. L., Lee, C. S., and Richardson, D. R. (2016) Redox cycling metals: pedaling their roles in metabolism and their use in the development of novel therapeutics. Biochim. Biophys. Acta 1863, 727–748
9. Yanatori, I., Tabuchi, M., Kawai, Y., Yasui, Y., Akagi, R., and Kishi, F. (2010) Heme and non-heme iron transporters in non-polarized and polarized cells. BMC Cell Biol. 11, 39
10. Raffin, S. B., Woo, C. H., Roost, K. T., Price, D. C., and Schmid, R. (1974) Intestinal absorption of hemoglobin iron-heme cleavage by mucosal heme oxygenase. J. Clin. Invest. 54, 1344 –1352
11. Lane, D. J., Bae, D. H., Merlot, A. M., Sahni, S., and Richardson, D. R. (2015) Duodenal cytochrome b (DCYTB) in iron metabolism: an update on function and regulation. Nutrients 7, 2274 –2296
12. Hurrell, R. (2010) Iron and malaria: absorption, efficacy and safety. Int. J. Vitam. Nutr. Res. 80, 279 –292
13. Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., and Hediger, M. A. (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388, 482– 488
14. Kishi, F., and Tabuchi, M. (1997) Complete nucleotide sequence of human NRAMP2 cDNA. Mol. Immunol. 34, 839 – 842
15. Yanatori, I., Yasui, Y., Noguchi, Y., and Kishi, F. (2015) Inhibition of iron uptake by ferristatin II is exerted through internalization of DMT1 at the plasma membrane. Cell Biol. Int. 39, 427– 434
16. Tabuchi, M., Yoshimori, T., Yamaguchi, K., Yoshida, T., and Kishi, F. (2000) Human NRAMP2/DMT1, which mediates iron transport across endosomal membranes, is localized to late endosomes and lysosomes in HEp-2 cells. J. Biol. Chem. 275, 22220 –22228
17. Tabuchi, M., Tanaka, N., Nishida-Kitayama, J., Ohno, H., and Kishi, F. (2002) Alternative splicing regulates the subcellular localization of divalent metal transporter 1 isoforms. Mol. Biol. Cell 13, 4371– 4387
18. Tabuchi, M., Yanatori, I., Kawai, Y., and Kishi, F. (2010) Retromer-me-diated direct sorting is required for proper endosomal recycling of the mammalian iron transporter DMT1. J. Cell Sci. 123, 756 –766
19. Wardrop, S. L., and Richardson, D. R. (1999) The effect of intracellular iron concentration and nitrogen monoxide on Nramp2 expression and non-transferrin-bound iron uptake. Eur. J. Biochem. 263, 41–49
20. Tenhunen, R., Marver, H. S., and Schmid, R. (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. U.S.A. 61, 748 –755
21. Shibahara, S., Müller, R., Taguchi, H., and Yoshida, T. (1985) Cloning and expression of cDNA for rat heme oxygenase. Proc. Natl. Acad. Sci. U.S.A. 82, 7865–7869
22. McCoubrey, W. K., Jr., Ewing, J. F., and Maines, M. D. (1992) Human heme oxygenase-2: characterization and expression of a full-length cDNA and evidence suggesting that the two HO-2 transcripts may differ by choice of polyadenylation signal. Arch. Biochem. Biophys. 295, 13–20
23. Maines, M. D., Trakshel, G. M., and Kutty, R. K. (1986) Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J. Biol. Chem. 261, 411– 419
24. Ghattas, M. H., Chuang, L. T., Kappas, A., and Abraham, N. G. (2002) Protective effect of HO-1 against oxidative stress in human hepatoma cell line (HepG2) is independent of telomerase enzyme activity. Int. J. Biochem. Cell Biol. 34, 1619 –1628
25. Paine, A., Eiz-Vesper, B., Blasczyk, R., and Immenschuh, S. (2010) Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochem. Pharmacol. 80, 1895–1903
26. Prawan, A., Kundu, J. K., and Surh, Y. J. (2005) Molecular basis of heme oxygenase-1 induction: implications for chemoprevention and chemo-protection. Antioxid. Redox Signal. 7, 1688 –1703
27. Liping, Z., Hongbo, S., Xiaohua, L., and Zhaopu, L. (2013) Gene regulation of iron-deficiency responses is associated with carbon monoxide and heme oxydase 1 in Chlamydomonas reinhardtii. PLoS ONE 8, e53835
28. Ferris, C. D., Jaffrey, S. R., Sawa, A., Takahashi, M., Brady, S. D., Barrow, R. K., Tysoe, S. A., Wolosker, H., Barañano, D. E., Doré, S., Poss, K. D., and Snyder, S. H. (1999) Haem oxygenase-1 prevents cell death by regulating cellular iron. Nat. Cell Biol. 1, 152–157
29. Watts, R. N., and Richardson, D. R. (2004) Differential effects on cellular iron metabolism of the physiologically relevant diatomic effector molecules, NO and CO, that bind iron. Biochim. Biophys. Acta 1692, 1–15
30. Li, C., Lönn, M. E., Xu, X., Maghzal, G. J., Frazer, D. M., Thomas, S. R., Halliwell, B., Richardson, D. R., Anderson, G. J., and Stocker, R. (2012) Sustained expression of heme oxygenase-1 alters iron homeostasis in nonerythroid cells. Free Radic. Biol. Med. 53, 366 –374
31. Huang, M. L., Becker, E. M., Whitnall, M., Suryo Rahmanto, Y., Ponka, P., and Richardson, D. R. (2009) Elucidation of the mechanism of mitochondrial iron loading in Friedreich’s ataxia by analysis of a mouse mutant. Proc. Natl. Acad. Sci. U.S.A. 106, 16381–16386
32. Ayer, A., Zarjou, A., Agarwal, A., and Stocker, R. (2016) Heme oxyge-nases in cardiovascular health and disease. Physiol. Rev. 96, 1449 –1508
33. Calabrese, V., Butterfield, D. A., Scapagnini, G., Stella, A. M., and Maines, M. D. (2006) Redox regulation of heat shock protein expression by signaling involving nitric oxide and carbon monoxide: relevance to brain aging, neurodegenerative disorders, and longevity. Antioxid. Redox Signal. 8, 444 – 477
34. Mustafa, A. K., Gadalla, M. M., and Snyder, S. H. (2009) Signaling by gasotransmitters. Sci. Signal. 2, re2
35. Parfenova, H., Leffler, C. W., Basuroy, S., Liu, J., and Fedinec, A. L. (2012) Antioxidant roles of heme oxygenase, carbon monoxide, and bilirubin in cerebral circulation during seizures. J. Cereb. Blood Flow Metab. 32, 1024 –1034
36. Shi, H., Bencze, K. Z., Stemmler, T. L., and Philpott, C. C. (2008) A cytosolic iron chaperone that delivers iron to ferritin. Science 320, 1207–1210
37. Yanatori, I., Yasui, Y., Tabuchi, M., and Kishi, F. (2014) Chaperone protein involved in transmembrane transport of iron. Biochem. J. 462, 25–37
38. Lane, D. J., and Richardson, D. R. (2014) Chaperone turns gatekeeper: PCBP2 and DMT1 form an iron-transport pipeline. Biochem. J. 462, e1–3
39. Yanatori, I., Richardson, D. R., Imada, K., and Kishi, F. (2016) Iron export through the transporter ferroportin 1 is modulated by the iron chaperone PCBP2. J. Biol. Chem. 291, 17303–17318
40. Swanson, M. S., and Dreyfuss, G. (1988) Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA-binding specificities. Mol. Cell. Biol. 8, 2237–2241
41. Makeyev, A. V., and Liebhaber, S. A. (2000) Identification of two novel mammalian genes establishes a subfamily of KH-domain RNA-binding proteins. Genomics 67, 301–316
42. Makeyev, A. V., and Liebhaber, S. A. (2002) The poly(C)-binding proteins: a multiplicity of functions and a search for mechanisms. RNA 8, 265–278
43. Leidgens, S., Bullough, K. Z., Shi, H., Li, F., Shakoury-Elizeh, M., Yabe, T., Subramanian, P., Hsu, E., Natarajan, N., Nandal, A., Stemmler, T. L., and Philpott, C. C. (2013) Each member of the poly-r(C)-binding protein 1 (PCBP) family exhibits iron chaperone activity toward ferritin. J. Biol. Chem. 288, 17791–17802
44. Dejgaard, K., and Leffers, H. (1996) Characterisation of the nucleic-acid-binding activity of KH domains. Different properties of different domains. Eur. J. Biochem. 241, 425– 431
45. Du, Z., Fenn, S., Tjhen, R., and James, T. L. (2008) Structure of a construct of a human poly(C)-binding protein containing the first and second KH domains reveals insights into its regulatory mechanisms. J. Biol. Chem. 283, 28757–28766
46. Choi, H. S., Hwang, C. K., Song, K. Y., Law, P. Y., Wei, L. N., and Loh, H. H. (2009) Poly(C)-binding proteins as transcriptional regulators of gene expression. Biochem. Biophys. Res. Commun. 380, 431– 436
47. Lane, D. J., Merlot, A. M., Huang, M. L., Bae, D. H., Jansson, P. J., Sahni, S., Kalinowski, D. S., and Richardson, D. R. (2015) Cellular iron uptake, trafficking and metabolism: key molecules and mechanisms and their roles in disease. Biochim. Biophys. Acta 1853, 1130 –1144
48. Gottlieb, Y., Truman, M., Cohen, L. A., Leichtmann-Bardoogo, Y., and Meyron-Holtz, E. G. (2012) Endoplasmic reticulum anchored heme-oxygenase 1 faces the cytosol. Haematologica 97, 1489 –1493
49. Muñoz-Sánchez, J., and Chánez-Cárdenas, M. E. (2014) A review on hemeoxygenase-2: focus on cellular protection and oxygen response. Oxid. Med. Cell Longev. 2014, 604981
50. Walter, B. L., Nguyen, J. H., Ehrenfeld, E., and Semler, B. L. (1999) Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements. RNA 5, 1570 –1585
51. Toyoda, H., Franco, D., Fujita, K., Paul, A. V., and Wimmer, E. (2007) Replication of poliovirus requires binding of the poly(rC) binding protein to the cloverleaf as well as to the adjacent C-rich spacer sequence between the cloverleaf and the internal ribosomal entry site. J. Virol. 81, 10017–10028
52. Burke, J. M., Cao, F., and Irving, P. E. (2000) High levels of E-/P-cadherin: correlation with decreased apical polarity of Na/K ATPase in bovine RPE cells in situ. Invest. Ophthalmol. Vis. Sci. 41, 1945–1952
53. Schrag, J. D., Bergeron, J. J., Li, Y., Borisova, S., Hahn, M., Thomas, D. Y., and Cygler, M. (2001) The structure of calnexin, an ER chaperone involved in quality control of protein folding. Mol. Cell 8, 633– 644
54. Kida, Y., Ohgiya, S., Mihara, K., and Sakaguchi, M. (1998) Membrane topology of NADPH-cytochrome P450 reductase on the endoplasmic reticulum. Arch. Biochem. Biophys. 351, 175–179
55. Erickson, J. W., Zhang, Cj., Kahn, R. A., Evans, T., and Cerione, R. A. (1996) Mammalian Cdc42 is a brefeldin A-sensitive component of the Golgi apparatus. J. Biol. Chem. 271, 26850 –26854
56. Ronnebaum, S. M., Ilkayeva, O., Burgess, S. C., Joseph, J. W., Lu, D., Stevens, R. D., Becker, T. C., Sherry, A. D., Newgard, C. B., and Jensen, M. V. (2006) A pyruvate cycling pathway involving cytosolic NADP-de-pendent isocitrate dehydrogenase regulates glucose-stimulated insulin secretion. J. Biol. Chem. 281, 30593–30602
57. Sugishima, M., Sato, H., Higashimoto, Y., Harada, J., Wada, K., Fukuyama, K., and Noguchi, M. (2014) Structural basis for the electron transfer from an open form of NADPH-cytochrome P450 oxidoreductase to heme oxygenase. Proc. Natl. Acad. Sci. U.S.A. 111, 2524 –2529
58. You, F., Sun, H., Zhou, X., Sun, W., Liang, S., Zhai, Z., and Jiang, Z. (2009) PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiq-uitin ligase AIP4. Nat. Immunol. 10, 1300 –1308
59. Murahashi, M., Simizu, S., Morioka, M., and Umezawa, K. (2016) Identification of poly(rC) binding protein 2 (PCBP2) as a target protein of immunosuppressive agent 15-deoxyspergualin. Biochem. Biophys. Res. Commun. 476, 445– 449
60. Gisk, B., Yasui, Y., Kohchi, T., and Frankenberg-Dinkel, N. (2010) Characterization of the haem oxygenase protein family in Arabidopsis thali-ana reveals a diversity of functions. Biochem. J. 425, 425– 434
61. Zhu, W., Wilks, A., and Stojiljkovic, I. (2000) Degradation of heme in Gram negative bacteria: the product of the hemO gene of Neisseria is a heme oxygenase. J. Bacteriol. 6783– 6790
62. Wilks, A., and Schmitt, M. P. (1998) Expression and characterization of a heme oxygenase (HmuO) from Corynebacterium diphtheria. Iron acquisition requires oxidative cleavage of the heme macrocycle. J. Biol. Chem. 273, 837– 841
63. Tenhunen, R., Marver, H. S., and Schmid, R. (1969) Microsomal heme oxygenase. Characterization of the enzyme. J. Biol. Chem. 244, 6388 – 6394
64. Schacter, B. A., Nelson, E. B., Marver, H. S., and Masters, B. S. (1972) Immunochemical evidence for an association of heme oxygenase with the microsomal electron transport system. J. Biol. Chem. 247, 3601–3607
65. Abate, A., Zhao, H., Wong, R. J., and Stevenson, D. K. (2007) The role of Bach1 in the induction of heme oxygenase by tin mesoporphyrin. Biochem. Biophys. Res. Commun. 354, 757–763
66. Becker, E., and Richardson, D. R. (2001) Frataxin: its role in iron metabolism and the pathogenesis of Friedreich’s ataxia. Int. J. Biochem. Cell Biol. 33, 1–10
67. Riemer, J., Hoepken, H. H., Czerwinska, H., Robinson, S. R., and Dringen, R. (2004) Colorimetric ferrozine-based assay for the quantitation of iron in cultured cells. Anal. Biochem. 331, 370 –375
68. Zähringer, J., Baliga, B. S., and Munro, H. N. (1976) Novel mechanism for translational control in regulation of ferritin synthesis by iron. Proc. Natl. Acad. Sci. U.S.A. 73, 857– 861
69. Aziz, N., and Munro, H. N. (1986) Both subunits of rat liver ferritin are regulated at a translational level by iron induction. Nucleic Acids Res. 14, 915–927
70. Sardana, M. K., and Kappas, A. (1987) Dual control mechanism for heme oxygenase: Tin(IV)–protoporphyrin potently inhibits enzyme activity while markedly increasing content of enzyme protein in liver. Proc. Natl. Acad. Sci. U.S.A. 84, 2464 –2468
71. Andrade, B. B., Araújo-Santos, T., Luz, N. F., Khouri, R., Bozza, M. T., Camargo, L. M., Barral, A., Borges, V. M., and Barral-Netto, M. (2010) Heme impairs prostaglandin E2 and TGF- production by human mononuclear cells via Cu/Zn superoxide dismutase: insight into the pathogenesis of severe malaria. J. Immunol. 185, 1196 –1204
72. Zukor, H., Song, W., Liberman, A., Mui, J., Vali, H., Fillebeen, C., Panto-poulos, K., Wu, T. D., Guerquin-Kern, J. L., and Schipper, H. M. (2009) HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues. J. Neurochem. 109, 776 –791
73. Sun, J., Loehr, T. M., Wilks, A., and Ortiz de Montellano, P. R. (1994) Identification of histidine 25 as the heme ligand in human liver heme oxygenase. Biochemistry 33, 13734 –13740
74. Ito-Maki, M., Ishikawa, K., Matera, K. M., Sato, M., Ikeda-Saito, M., and Yoshida, T. (1995) Demonstration that histidine 25, but not histidine-132, is the axial heme ligand in rat heme oxygenase-1. Arch. Biochem. Biophys. 317, 253–258
75. Zhou, W. P., Zhong, W. W., Zhang, X. H., Ding, J. P., Zhang, Z. L., and Xia, Z. W. (2009) Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1. Int. J. Mol. Med. 23, 379 –387
76. Abraham, N. G., and Kappas, A. (2008) Pharmacological and clinical aspects of heme oxygenase. Pharmacol. Rev. 60, 79 –127
77. Fujimura, K., Kano, F., and Murata, M. (2008) Identification of PCBP2, a facilitator of IRES-mediated translation, as a novel constituent of stress granules and processing bodies. RNA 14, 425– 431
78. Huber, Iii W. J., Scruggs, B. A., and Backes, W. L. (2009) C-terminal membrane spanning region of human heme oxygenase-1 mediates a time-dependent complex formation with cytochrome P450 reductase. Biochemistry. 48, 190 –197
79. Yoshida, T., and Migita, C. T. (2000) Mechanism of heme degradation by heme oxygenase. J. Inorg. Biochem. 82, 33– 41
80. Sugishima, M., Sakamoto, H., Kakuta, Y., Omata, Y., Hayashi, S., Noguchi, M., and Fukuyama, K. (2002) Crystal structure of rat apo-heme oxygenase-1 (HO-1): mechanism of heme binding in HO-1 inferred from structural comparison of the apo and heme complex forms. Biochemistry 41, 7293–7300
81. Sakamoto, H., Omata, Y., Hayashi, S., Harada, S., Palmer, G., and Noguchi, M. (2002) The reactivity of -hydroxyhaem and verdohaem bound to haem oxygenase-1 to dioxygen and sodium dithionite. Eur. J. Biochem. 269, 5231–5239
82. Higashimoto, Y., Sato, H., Sakamoto, H., Takahashi, K., Palmer, G., and Noguchi, M. (2006) The reactions of heme- and verdoheme-heme oxygenase-1 complexes with FMN-depleted NADPH-cytochrome P450 reductase. Electrons required for verdoheme oxidation can be transferred through a pathway not involving FMN. J. Biol. Chem. 281, 31659–31667
83. Lemberg, R., and Legge, J. W. (1949) Hematin Compounds and Bile Pigments, Their Constitution, Metabolism and Function, p. 93. Interscience Publishers, New York
84. Higashimoto, Y., Sakamoto, H., Hayashi, S., Sugishima, M., Fukuyama, K., Palmer, G., and Noguchi, M. (2005) Involvement of NADPH in the interaction between heme oxygenase-1 and cytochrome P450 reductase. J. Biol. Chem. 280, 729 –737
85. Cairo, G., Bernuzzi, F., and Recalcati, S. (2006) A precious metal: iron, an essential nutrient for all cells. Genes Nutr. 1, 25–39
86. Ghanem, L. R., Kromer, A., Silverman, I. M., Chatterji, P., Traxler, E., Penzo-Mendez, A., Weiss, M. J., Stanger, B. Z., and Liebhaber, S. A. (2015) The poly(C) binding protein pcbp2 and its retrotransposed derivative pcbp1 are independently essential to mouse development. Mol. Cell. Biol. 36, 304 –319
87. Sugishima, M., Hagiwara, Y., Zhang, X., Yoshida, T., Migita, C. T., and Fukuyama, K. (2005) Crystal structure of dimeric heme oxygenase-2 fromSynechocystissp.PCC6803incomplexwithheme.Biochemistry44, 4257–4266
88. Hwang, H. W., Lee, J. R., Chou, K. Y., Suen, C. S., Hwang, M. J., Chen, C., Shieh, R. C., and Chau, L. Y. (2009) Oligomerization is crucial for the stability and function of heme oxygenase-1 in the endoplasmic reticulum. J. Biol. Chem. 284, 22672–22679
89. Gamarnik, A. V., and Andino, R. (2000) Interactions of viral protein 3CD and poly(rC) binding protein with the 5 untranslated region of the poliovirus genome. J. Virol. 74, 2219 –2226
90. Calò, L. A., Savoia, C., Davis, P. A., Pagnin, E., Ravarotto, V., and Maio-lino, G. (2015) Relationship between NOX4 level and angiotensin II signaling in Gitelman’s syndrome. Implications with hypertension. Int. J. Clin. Exp. 8, 7487–7496
91. Choi, K., Kim, J. H., Li, X., Paek, K. Y., Ha, S. H., Ryu, S. H., Wimmer, E., and Jang, S. K. (2004) Identification of cellular proteins enhancing activities of internal ribosomal entry sites by competition with oligodeoxy-nucleotides. Nucleic Acids Res. 32, 1308 –1317
92. West, A. R., and Oates, P. S. (2008) Mechanisms of heme iron absorption: current questions and controversies. World J. Gastroenterol. 14, 4101– 4110
93. Lad, L., Schuller, D. J., Shimizu, H., Friedman, J., Li, H., Ortiz de Montellano, P. R., and Poulos, T. L. (2003) Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1. J. Biol. Chem. 278, 7834 –7843
94. Liuzzi, J. P., Aydemir, F., Nam, H., Knutson, M. D., and Cousins, R. J. (2006) Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc. Natl. Acad. Sci. U.S.A. 103, 13612–13617
95. Xiao, G., Wan, Z., Fan, Q., Tang, X., and Zhou, B. (2014) The metal transporter ZIP13 supplies iron into the secretory pathway in Drosophila melanogaster. eLife 3, e03191
96. Shaw, G. C., Cope, J. J., Li, L., Corson, K., Hersey, C., Ackermann, G. E., Gwynn, B., Lambert, A. J., Wingert, R. A., Traver, D., Trede, N. S., Barut, B. A., Zhou, Y., Minet, E., Donovan, A., et al. (2006) Mitoferrin is essential for erythroid iron assimilation. Nature 440, 96–100
97. York, J. D., Saffitz, J. E., and Majerus, P. W. (1994) Inositol polyphosphate 1-phosphatase is present in the nucleus and inhibits DNA synthesis. J. Biol. Chem. 269, 19992–19999
98. Ziman, M., Preuss, D., Mulholland, J., O’Brien, J. M., Botstein, D., and Johnson, D. I. (1993) Subcellular localization of Cdc42p, a Saccharomyces cerevisiae GTP-binding protein involved in the control of cell polarity. Mol. Biol. Cell 12, 1307–1316
99. Gao, J., and Richardson, D. R. (2001) The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents, IV: The mechanisms involved in inhibiting cell-cycle progression. Blood 98, 842– 850
100. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) Protein measurement with the folin phenol reagent. J. Biol. Chem. 193, 265–275