Human iron regulatory protein 2 is easily cleaved in its specific domain: Consequences for the haem binding properties of the protein

Biochemical Journal

Volumn 408, Issue 3, 2007, Pages 429-439

  Dycke, Camille ^a,b,c,h   Bougault, Catherine ^c,d   Gaillard, Jacques ^e   Andrieu, Jean Pierre ^c,d   Pantopoulos, Kostas ^f,g   Moulis, Jean Marc ^b,c  

^a CEA GRENOBLE   (France)

^b CNRS   (France)

^c UNIV GRENOBLE ALPES   (France)

^d INSTITUT DE BIOLOGIE STRUCTURALE   (France)

^e Service de Chimie Inorganique et Biologique   (France)

^f MCGILL UNIVERSITY   (Canada)

^g MCGILL UNIVERSITY   (Canada)

^h Department of Genetic and Molecular Toxicology   (United Kingdom)

Author keywords

EPR; Haem binding protein; Haem regulatory motif (HRM); Iron regulatory protein 2 (IRP2); NMR spectroscopy; Proteolysis

Indexed keywords

AMINO ACIDS; DEGRADATION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTEOLYSIS; RNA; TRANSCRIPTION;

AXIAL LIGANDS; HAEM BINDING PROTEINS; HAEM REGULATORY MOTIF; IRON REGULATORY PROTEINS;

PROTEINS;

HEME; IRON REGULATORY PROTEIN 2;

ABSORPTION SPECTROSCOPY; ARTICLE; CANCER CELL; CONTROLLED STUDY; HUMAN; HUMAN CELL; LUNG CANCER; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN INTERACTION;

MAMMALIA;

EID: 37549024201     PISSN: 02646021     EISSN: None     Source Type: Journal    
DOI: 10.1042/BJ20070983     Document Type: Article

References (43)

1. Hentze, M. W., Muckenthaler, M. U. and Andrews, N. C. (2004) Balancing acts: molecular control of mammalian iron metabolism. Cell 117, 285-297
2. Wallander, M. L., Leibold, E. A. and Eisenstein, R. S. (2006) Molecular control of vertebrate iron homeostasis by iron regulatory proteins. Biochim. Biophys. Acta 1763, 668-689
3. Wingert, R. A., Galloway, J. L., Barut, B., Foott, H., Fraenkel, P., Axe, J. L., Weber, G. J., Dooley, K., Davidson, A. J., Schmid, B. et al. (2005) Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature 436, 1035-1039
4. Sposi, N. M., Cianetti, L., Tritarelli, E., Pelosi, E., Militi, S., Barberi, T., Gabbianelli, M., Saulle, E., Kühn, L., Peschle, C. and Testa, U. (2000) Mechanisms of differential transferrin receptor expression in normal hematopoiesis. Eur. J. Biochem. 267, 6762-6774
5. Schranzhofer, M., Schifrer, M., Cabrera, J. A., Kopp, S., Chiba, P., Beug, H. and Müllner, E. W. (2006) Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis. Blood 107, 4159-4167
6. LaVaute, T., Smith, S., Cooperman, S., Iwai, K., Land, W., Meyron-Holtz, E., Drake, S. K., Miller, G., Abu-Asab, M., Tsokos, M. et al. (2001) Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat. Genet. 27, 209-214
7. Cooperman, S. S., Meyron-Holtz, E. G., Olivierre-Wilson, H., Ghosh, M. C., McConnell, J. P. and Rouault, T. A. (2005) Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. Blood 106, 1084-1091
8. Galy, B., Ferring, D., Minana, B., Bell, O., Janser, H. G., Muckenthaler, M., Schumann, K. and Hentze, M. W. (2005) Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2). Blood 106, 2580-2589
9. Smith, S. R., Ghosh, M. C., Ollivierre-Wilson, H., Hang Tong, W. and Rouault, T. A. (2006) Complete loss of iron regulatory proteins 1 and 2 prevents viability of murine zygotes beyond the blastocyst stage of embryonic development. Blood Cells Mol. Dis. 36, 283-287
10. Galy, B., Holter, S. M., Klopstock, T., Ferring, D., Becker, L., Kaden, S., Wurst, W., Grone, H. J. and Hentze, M. W. (2006) Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse. Nat. Genet. 38, 967-970
11. Meyron-Holtz, E. G., Ghosh, M. C. and Rouault, T. A. (2004) Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science 306, 2087-2090
12. Meyron-Holtz, E. G., Ghosh, M. C., Iwai, K., LaVaute, T., Brazzolotto, X., Berger, U. V., Land, W., Ollivierre-Wilson, H., Grinberg, A., Love, P. and Rouault, T. A. (2004) Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J. 23, 386-395
13. Samaniego, F., Chin, J., Iwai, K., Rouault, T. A. and Klausner, R. D. (1994) Molecular characterization of a second-responsive element binding protein, iron regulatory protein 2. Structure, function and post-transcriptional regulation. J. Biol. Chem. 269, 30904-30910
14. Iwai, K., Klausner, R. D. and Rouault, T. A. (1995) Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2. EMBO J. 14, 5350-5357
15. Iwai, K., Drake, S. K., Wehr, N. B., Weissman, A. M., LaVaute, T., Minato, N., Klausner, R. D., Levine, R. L. and Rouault, T. A. (1998) Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins. Proc. Natl. Acad. Sci. U.S.A. 95, 4924-4928
16. Kang, D. K., Jeong, J., Drake, S. K., Wehr, N. B., Rouault, T. A. and Levine, R. L. (2003) Iron regulatory protein 2 as iron sensor. Iron-dependent oxidative modification of cysteine. J. Biol. Chem. 278, 14857-14864
17. Yamanaka, K., Ishikawa, H., Megumi, Y., Tokunaga, F., Kanie, M., Rouault, T. A., Morishima, I., Minato, N., Ishimori, K. and Iwai, K. (2003) Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2. Nat. Cell Biol. 5, 336-340
18. Jeong, J., Rouault, T. A. and Levine, R. L. (2004) Identification of a heme-sensing domain in iron regulatory protein 2. J. Biol. Chem. 279, 45450-45454
19. Ishikawa, H., Kato, M., Hori, H., Ishimori, K., Kirisako, T., Tokunaga, F. and Iwai, K. (2005) Involvement of heme regulatory motif in heme-mediated ubiquitination and degradation of IRP2. Mol. Cell 19, 171-181
20. Hanson, E. S., Rawlins, M. L. and Leibold, E. A. (2003) Oxygen and iron regulation of iron regulatory protein 2. J. Biol. Chem. 278, 40337-40342
21. Wang, J., Chen, G., Muckenthaler, M., Galy, B., Hentze, M. W. and Pantopoulos, K. (2004) Iron-mediated degradation of IRP2, an unexpected pathway involving a 2-oxoglutarate-dependent oxygenase activity. Mol. Cell. Biol. 24, 954-965
22. Tabor, S. (1990) in Current Protocols in Molecular Biology (Ausubel, F. A., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A. and Struhl, K., eds), pp 16.2.1-16.2.11, Greene Publishing and Wiley-Interscience, New York
23. Martelli, A. and Moulis, J.-M. (2004) Zinc and cadmium specifically interfere with RNA-binding activity of human iron regulatory protein 1. J. Inorg. Biochem. 98, 1413-1420
24. Wang, J. and Pantopoulos, K. (2002) Conditional derepression of ferritin synthesis in cells expressing a constitutive IRP1 mutant. Mol. Cell. Biol. 22, 4638-4651
25. Piotto, M., Saudek, V. and Sklenar, V. (1992) Gradient-tailored excitation for single-quantum NMR-spectroscopy of aqueous-solutions. J. Biomol. NMR 2, 661-665
26. Hwang, T. L. and Shaka, A. J. (1995) Water suppression that works - excitation sculpting using arbitrary wave-forms and pulsed-field gradients. J. Magn. Reson. A 112, 275-279
27. Schanda, P., Forge, V. and Brutscher, B. (2006) HET-SOFAST NMR for fast detection of structural compactness and heterogeneity along polypeptide chains. Magn. Reson. Chem. 44, S177-S184
28. Brazzolotto, X., Gaillard, J., Pantopoulos, K., Hentze, M. W. and Moulis, J.-M. (1999) Human cytoplasmic aconitase (iron regulatory protein 1) is converted into its [3Fe-4S] form by hydrogen peroxide in vitro but is not activated for iron-responsive element binding. J. Biol. Chem. 274, 21625-21630
29. Martelli, A., Salin, B., Dycke, C., Louwagie, M., Andrieu, J.-P., Richaud, P. and Moulis, J.-M. (2007) Folding and turnover of human iron regulatory protein 1 depend on its subcellular localization. FEBS J. 274, 1083-1092
30. Dupuy, J., Volbeda, A., Carpentier, P., Darnault, C., Moulis, J.-M. and Fontecilla-Camps, J. C. (2006) Crystal structure of human iron regulatory protein 1 as cytosolic aconitase. Structure 14, 129-139
31. Guo, B., Yu, Y. and Leibold, E. A. (1994) Iron regulates cytoplasmic levels of a novel iron-responsive element-binding protein without aconitase activity. J. Biol. Chem. 269, 24252-24260
32. Goessling, L. S., Mascotti, D. P. and Thach, R. E. (1998) Involvement of heme in the degradation of iron-regulatory protein 2. J. Biol. Chem. 273, 12555-12557
33. de Villiers, K. A., Kaschula, C. H., Egan, T. J. and Marques, H. M. (2007) Speciation and structure of ferriprotoporphyrin IX in aqueous solution: spectroscopic and diffusion measurements demonstrate dirnerization, but not mu-oxo dimer formation. J. Biol. Inorg. Chem. 12, 101-117
34. Qi, Z., Hamza, I. and O'Brian, M. R. (1999) Heme is an effector molecule for iron-dependent degradation of the bacterial iron response regulator (Irr) protein. Proc. Natl. Acad. Sci. U.S.A. 96, 13056-13061
35. Suzuki, H., Tashiro, S., Hira, S., Sun, J., Yamazaki, C., Zenke, Y., Ikeda-Saito, M., Yoshida, M. and Igarashi, K. (2004) Heme regulates gene expression by triggering Crm1-dependent nuclear export of Bach1. EMBO J. 23, 2544-2553
36. Dawson, J. H., Andersson, L. A. and Sono, M. (1983) The diverse spectroscopic properties of ferrous cytochrome P-450-CAM ligand complexes. J. Biol. Chem. 258, 13637-13645
37. Stuehr, D. J. and Ikeda-Saito, M. (1992) Spectral characterization of brain and macrophage nitric oxide synthases. Cytochrome P-450-like hemeproteins that contain a flavin semiquinone radical. J. Biol. Chem. 267, 20547-20550
38. Sono, M. and Dawson, J. H. (1982) Formation of low spin complexes of ferrie cytochrome P-450-CAM with anionic ligands. Spin state and ligand affinity comparison to myoglobin. J. Biol. Chem. 257, 5496-5502
39. Zhang, L. and Guarente, L. (1995) Heme binds to a short sequence that serves a regulatory function in diverse proteins. EMBO J. 14, 313-320
40. Rafie-Kolpin, M., Chefalo, P. J., Hussain, Z., Hahn, J., Uma, S., Matts, R. L. and Chen, J. J. (2000) Two heme-binding domains of heme-regulated eukaryotic initiation factor-2α kinase. N terminus and kinase insertion. J. Biol. Chem. 275, 5171-5178
41. Guo, B., Phillips, J. D., Yu, Y. and Leibold, E. A. (1995) Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J. Biol. Chem. 270, 21645-21651
42. Kim, S., Wing, S. S. and Ponka, P. (2004) S-nitrosylation of IRP2 regulates its stability via the ubiquitin-proteasome pathway. Mol. Cell. Biol. 24, 330-337
43. Wang, J. and Pantopoulos, K. (2005) The pathway for IRP2 degradation involving 2-oxoglutarate-dependent oxygenase(s) does not require the E3 ubiquitin ligase activity of pVHL. Biochim. Biophys. Acta 1743, 79-85