Abstract
The complexity of eukaryotic gene regulation is slowly being resolved. What has become clear is that transcriptional regulation is a multi-step process that involves the assembly of macromolecular complexes. This review will discuss the biology of the ETS family transcription factor PU.1, with emphasis on its interactions with two members of the Interferon Regulatory Factor (IRF) family, interferon consensus sequence binding protein (ICSBP) and IRF-4. The role of these interactions in transcriptional regulation is discussed, with respect to DNA binding motifs, protein-protein interaction and phosphorylation states that modulate PU.1/IRF interactions. Furthermore, potential transcriptional mechanisms for several genes are discussed, focusing on genes involved in innate immunity. Data from these studies suggest at least four distinct paradigms for transcriptional regulation by an ETS protein in conjunction with either ICSBP or IRE-4. These paradigms may describe regulatory mechanisms common to many distinct transcription factor families. Last, recent data from several laboratories have now documented the expression of ICSBP and IRF-4 in a range of cell types. These data suggest that ICSBP and IRF-4 may serve functions within these cell types that are distinct from their previously recognized functions.
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References
Driggers, P. H., Ennist, D. L., Gleason, S. L., Mak, W.-H., Marks, M. S., Levi, B.-Z., et al. (1990) An interferon γ-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. PNAS 87, 3743–3747.
Eisenbeis, C. F., Singh, H., and Storb, U. (1995) Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator. Genes and Development 9, 1377–1387.
Nelsen, B., Tian, G., Erman, B., Gregoire, J., Maki, R., Graves, B., and Sen, R. (1993) Regulation of lymphoid-specific immunoglobulin mu heavy chain gene enhancer by ETS-domain proteins. Science 261, 82–86.
Eklund, E. A., A. J., and R. K. (1998) PU.1, Interferon Regulatory Factor 1, and Interferon Consensus Sequence Binding Protein Cooperate to increase gp91phox expression. J. Biol. Chem. 273, 13957–13965.
Zhang, D., Hetherington, J., Chen, H., and Tenen, D. G. (1994) The macrophage transcription factor PU.1 directs tissue-specific expression of the macrophage colony-stimulating factor receptor. Mol. Cell. Biol. 14, 373–381.
Eisenbeis, C. F., Singh, H., and Storb, U. (1993) PU.1 is a component of a multiprotein complex which binds an essential site in the murine immunoglobulin lambda 2–4 enhancer. Mol. Cell. Biol. 13, 6452–6461.
Pongubala, J. M., Nagulapalli, S., Klemsz, M. J., McKercher, S. R., Maki, R. A., and Atchison, M. L. (1992) PU.1 recruits a second nuclear factor to a site important for immunoglobulin κ 3′ enhancer activity. Mol. Cell. Biol. 12, 368–378.
Himmelmann, A., Riva, A., Wilson, G. L., Lucas, B. P., Thevenin, C., and Kehri, J. H. (1997) PU.1/Pip and basic helix loop helix zipper transcription factors interact with binding sites in the CD20 promoter to help confer lineage—and stage-specific expression of CD20 in B lymphocytes. Blood 90, 3984–3995.
Wasylyk, B., Hahn, S. L., and Giovane, A. (1993) The Ets family of transcription factors. Eur. J. Biochem. 277, 7–18.
Moreau-Gachelin, F. (1994) Spi-1/PU.1: an oncogene of the Ets family. Biochim. Biophys. Acta 1198, 149–163.
Fisher, R. C., and Scott, E. W. (1998) Role of PU.1 in hematopoiesis. Stem Cells 16, 25–37.
Szymczyna, B. R., and Arrowsmith, C. H. (2000) DNA-binding specificity studies of 4 ETS proteins supports an “indirect read-out” mechanism of protein-DNA recognition. J. Biol. Chem. published June 23, 2000 as 10.1074/jbc.M004294200.
John, S., Reeves, R. B., Lin, X.-J., Child, R., Leiden, J. M., Thompson, C. B., and Leonard, W. J. (1995) Regulation of cell-type-specific Interleukin-2 receptor α-chain gene expression: protential role of physical interaction between Elf-1, HMG-I(Y), and NF-κB family proteins. Mol. Cell. Biol. 15, 1786–1796.
Thomas, R. S., Tymma, M. J., McKinlay, L. H., Shannon, M. F., Seth, A., and Kola, I. (1997) ETS1, NF-κB and AP1 synergistically transactivate the human GM-CSF promoter. Oncogene 14, 2845–2855.
Hagemeier, C., Bannister, A. J., Cook, A., and Kouzarides, T. (1993) The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. PNAS 90, 1580–1584.
Yamamoto, H., Kihara-Negishi, F., Yamada, T., Hashimoto, Y., and Oikawa, T. (1998) Physical and functional interactions between the transcription factor PU.1 and the coactivator CBP. Oncogene 18, 1495–1501.
Pongubala, J. M. R., Van Beveren, C., Nagulapalli, S., Klemsz, M. J., McKercher, S. R., Maki, R. A., and Atchison, M. A. (1993) Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. Science 259, 1622–1625.
Amaravadi, L., and Klemsz, M. J. (1999) DNA methylation and chromatin structure regulate PU.1 expression. DNA Cell. Biol. 18, 875–884.
Su, G. H., Ip, H. S., Cobb, B. S., Lu, M. M., Chen, H. M., and Simon, M. C. (1996) The ETS protein Spi-B is expressed exclusively in B cells and T cells during development. J. Exp. Med. 184, 203–214.
Bemark, M., Martensson, A., Liberg, D. and Leanderson, T. (1999) Spi-C, a novel Ets protein that is temporally regulated during B lymphocyte development. J. Biol. Chem. 274, 10259–10267.
Kodandapani, R., Pio, F., Ni, C.-Z., Piccialli, G., Klemsz, M., McKercher, S., Maki, R. A. and Ely, K. R. (1996) A new pattern for helix-turn-helix recognition revealed by the PU.1 ETS-domain-DNA complex. Nature 380, 456–460.
Pio, F., Kodandapani, R., Ni, C.-Z., Shepard, W., Klemsz, M., McKercher, S. R., Maki, R. A., and Ely, K. R. (1996) New insights on DNA recognition by ets proteins from the crystal structure of PU.1 ETS domain-DNA complex. J. Biol. Chem. 271, 23329–23337.
Moreau-Gachelin, F., Tavitian, A., and Tambourin, P. (1988) Spi-1 is a putative oncogene in virally induced murine erythroleukemias. Nature 331, 272–280.
Scott, E. W., Simon, M. C., Anastasi, J., and Singh, H. (1994) Requirement of the transciption factor PU.1 in the development of multiple hematopoietic lineages. Science 265, 1573–1577.
DeKoter, R. P., and Singh, H., 2000. Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science 288, 1439–1441.
Inaba, T., Gotoda, T., Ishibashi, S., Harada, K., Ohsuga, J.-I., Ohashi, K., Yazaki, Y., and Yamada, N. (1995) Transcription factor PU.1 mediates induction of c-fms in vascular smooth muscle cells: a mechanism for phenotypic change to phagocytic cells. Mol. Cell. Biol. 16, 2264–2273.
Pahl, H. L., Scheibe, R. J., Zhang, D. E., Chen, H. M., Galson, D. L., Maki, R. A., and Tenen, D. G. (1993) The proto-oncogene PU.1 regulates expression of the myeloid-specific CD11b promoter. J. Biol. Chem. 268, 5014–5020.
Buras, J. A., Monks, B. G., and Fenton, M. J. (1994) The NF-βA-binding element, not an overlapping NF-IL-6-binding element, is required for maximal IL-1β gene expression. J. Immunol. 152, 4444–4454.
Kominato, Y., Galson, D., Waterman, W. R., Webb, A. C., and Auron, P. E. (1995) Monocyte expression of the human prointerleukin 1 beta gene (IL-1β) is dependent on promoter sequences which bind the hematopoietic transcription factor Spi-1/PU.1. Mol. Cell. Biol. 15, 59–68.
Suzuki, S., Kumatori, A., Haagen, I.-A., Fuji, Y., Sadat, M. A., Jun, H. L., Tsuji, Y., Roos, D., and Nakamura, M. (1998) PU.1 as an essential activator for the expression of gp91phox gene in human peripheral neutrophils, monocytes, and B lymphocytes. PNAS 95, 6085–6090.
Moulton, K. S., Semple, K., Wu, H., and Glass, C. (1994) Cell-specific expression of the macrophage scavenger receptor gene is dependent on PU.1 and a composite AP-1/ets motif. Mol. Cell. Biol. 14, 4408–4418.
Egan, B. S., Lanes, K. B., and Shepherd, V. L. (1999) PU.1 and USF are required for macrophage-specific mannose receptor promoter activity. J. Biol. Chem. 274, 9098–9107.
Nagulapalli, S., Pongubala, J. M. R., and Atchison, M. L. (1995) Multiple proteins physically interact with PU.1. J. Immunol. 155, 4330–4338.
Bassuk, A. G., Anandappa, R. T., and Leiden, J. M. (1997) Physical interactions between Ets and NF-κB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells. J. Virol. 71, 3563–3573.
Behre, G., Whitmarsh, A. J., Coghlan, M. P., Hoang, T., Carpenter, C. L., Zhang, D.-E., Davis, R. J., and Tenen, D. G. (1999) c-jun is a c-Jun NH2-terminal kinase-independent coactivator of the PU.1 transcription factor. J. Biol. Chem. 274, 4939–4946.
Yang, Z., Wara-aswapati, N., Chen, C., Tsukada, J., and Auron, P. E., 2000. NF-IL6 (C/EBPβ) vigorously activates illb gene expression via a Spi-1 (PU.1) protein-protein tether. J. Biol. Chem. 275, 21272–21277.
Borras, F. E., Lloberas, J., Maki, R. A., and Celada, A. (1995) Repression of I-Aβ gene expression by the transcription factor PU.1. J. Biol. Chem. 270, 24385–24391.
Westermarck, J., Seth, A., and Kahari, V.-M. (1997) Differential regulation of interstitial collagenase (MMP-1) gene expression by ETS transcription factors. Oncogene 14, 2651–2660.
Lopez-Rodriguez, C., and Corbi, A. L. (1997) PU.1 negatively regulates the CD11c integrin gene promoter through recognition of the major transcriptional start site. Eur. J. Immunol. 27, 1843–1847.
Henkel, G. W., McKercher, S. R., Leenen, P. J. M. and Maki, R. A. (1999) Commitment to the monocytic lineage occurs in the absence of the transcription factor PU.1. Blood 93, 2849–2858.
Anderson, K. L., Smith, K. A., Conners, K., McKercher, S. R., Maki, R. A., and Torbett, B. E. (1998) Myeloid development is selectively disrupted in PU.1 null mice. Blood 91, 3702–3710.
McKercher, S. R., Torbett, B. E., Anderson, K. L., Henkel, G. W., Vestal, D. J., Baribault, H., Klemsz, M., Feeney, A. J., Wu, G. E., Paige, C. J., and Maki, R. A. (1996) Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO J. 15, 5647–5658.
Tondravi, M. M., McKercher, S. R., Anderson, K., Erdmann, J. M., Quiroz, M., Maki, R., and Teitelbaum, S. L. (1997) Osteopetrosis in mice lacking haematopietic transcription factor PU.1. Nature 386, 81–84.
Moreau-Gachelin, F., Wendling, F., Molina, T., Denis, N., Titeux, M., Grimber, G., Briand, P., Vainchenker, W., and Tavitian, A. (1996) Spi-1/PU.1 transgenic mice develop multistep erythroleukemias. Mol. Cell. Biol. 16, 2453–2463.
Fisher, R. C., Olson, M. C., Pongubala, J. M. R., Perkel, J. M., Atchison, M. L., Scott, E. W., and Simon, M. C. (1998) Normal myeloid development requires both the glutamine-rich transactivation domain and the PEST region of transcription factor PU.1 but not the potent acidic transactivation domain. Mol. Cell. Biol. 18, 4347–4357.
Celada, A., Borras, F. E., Soler, C., Lloberas, J., Klemsz, M., van Beveren, C., McKercher, S., and Maki, R. A. (1996) The transcription factor PU.1 is involved in macrophage proliferation. J. Exp. Med. 184, 61–69.
Lodie, T. A., Savedra, Jr., R., Golenbock, D. T., Van Beveren, C. P., Maki, R. A., and Fenton, M. J. (1997) Stimulation of macrophages by lipopolysaccharide alters the phosphorylation state, conformation, and function of PU.1 via activation of casein kinase II. J. Immunol. 158, 1848–1856.
Buras, J. A., Reensta, W. R., and Fenton, M. J. (1995) The NFβA, a factor required for maximal IL-1β gene expression is identical to the ets family member PU.1. Evidence for structural alteration following LPS activation. Mol. Immunol. 32, 541–555.
Pongubala, J. M. R., and Atchison, M. L. (1997) PU.1 can participate in an active enhancer complex without its transcriptional activation domain. PNAS 94, 127–132.
Stark, G. R., Kerr, I. M., Williams, B. R. G., Silverman, R. H. and Schreiber, R. D. (1998) How cells respond to interferons. Ann. Rev. Biochem. 67, 227–264.
Fenton, M. J., Vermeulen, M. W., Kim, S., Burdick, M., Strieter, R. M., and Kornfeld, H. (1997) Induction of gamma interferon production in human alveolar macrophages by Mycobacterium tuberculosis. Infect. Immun. 65, 5149–5156.
Fultz, M. J., Barber, S. A., Dieffenbach, C. W., and Vogel, S. N. (1993) Induction of IFN-γ in macrophages by lipopolysaccharide. Int. Immunol. 5, 1383–1392.
Yamagata, T., Nishida, J., Tanaka, T., Sakai, R., Mitani, K., Yoshida, M., Taniguchi, T., Yazaki, Y., and Hirai, H. (1996) A novel interferon regulatory factor family transcription factor, ICSAT/Pip/LSIRF, that negatively regulates the activity of interferon-regulated genes. Mol. Cell. Biol. 16, 1283–1294.
Matsuyama, T., Grossman, A., Mittrucker, H.-W., Siderovski, D. P., Kiefer, F., Kawakami, T., Richardson, C. D., Taniguchi, T., Yoshinaga, S. K., and Mak. T. (1995) Molecular cloning of LSIRF, a lymphoid-specific member of the interferon regulatory factor family that binds the interferon-stimulated response element (ISRE). Nuc. Acids Res. 23, 2127–2136.
Au, W.-C., Moore, P., Lowther, W., Juang, Y.-T., and Pitha, P. M. (1995) Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes. PNAS 92, 11657–11661.
Nguyen, H., Hiscott, J., and Pitha, P. M. (1997) The growing family of interferon regulatory factors. Cytokine Growth Factor Rev. 8, 293–312.
Mamane, Y., Heybroeck, C., Genin, P., Algarte, M., Servant, M. J., LePage, C., DeLuca, C., Kwon, H., Lin, R., and Hiscott, J. (1999) Interferon regulatory factors: The next generation. Gene 237, 1–14.
Searles, R. P., Bergquam, E. P., Axthelm, M. K., and Wong, S. W. (1999) Sequence and genomic analysis of a Rhesus macaque rhadinovirus with similarity to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8. J. Virol. 73, 3040–3053.
Yabu, T., Hirose, H., Katagiri, A., Aoki, T., and Yamamoto, E. (1998) Molecular cloning of a novel interferon regulatory factor in Japanese flounder, Paralichthys olivaceus. Mol. Mar. Biol. Biotechnol. 7, 138–144.
Fujita, T., Sakakibara, J., Sudo, Y., Miyamoto, M., Kimura, Y., and Tanaguguchi, T. (1988) Evidence for a nuclear factor(s), IRF-1, mediating induction and silencing properties to human IFN-β gene regulatory elements. EMBO J. 7, 3397–3405.
Harada, H., Fujita, T., Miyamoto, M., Kimura, Y., Maruyama, M., Furia, A., Miyata, T., and Taniguchi, T. (1989) Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind the same regulatory elements of IFN-β and IFN-inducible genes. Cell 58, 729–739.
Nguyen, H., Teskey, L., Lin, R., and Hiscott, J. (1999) Identification of the secretory leukocyte protease inhibitor (SLPI) as a target of IRF-1 regulation. Oncogene 18, 5455–5463.
Jesse, T. L., LaChance, R., Iademarco, M. F., and Dean, D. C. (1998) Interferon regulatory factor-2 is a transcriptional activator in muscle where it regulates expression of vascular cell adhesion molecule-1. J. Cell. Biol. 140, 1265–1276.
Salkowski, C. A., Kopydlowski, K., Blanco, J., Cody, M. J., McNally, R., and Vogel, S. N. (1999) IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice. J. Immunol. 163, 1529–1536.
Vaughan, P. S., Aziz, F., van Wijnen, A. J., Wu, S., Harada, H., Taniguchi, T., Soprano, K. J., Stein, J. L., and Stein, G. S. (1995) Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2. Nature 377, 362–365.
Luo, W., and Skalnik, D. G. (1996) Interferon Regulatory Factor-2 directs trancription from the gp91phox promoter. J. Biol. Chem. 271, 23445–23451.
Gobin, S. J. P., van Zutphen, M., Woltman, A. M., and van den Elsen, P. J. (1999) Transactivation of classical and nonclassical HLA class I genes through the IFN-stimulated response element. J. Immunol. 163, 1428–1434.
Escalante, C. R., Yie, J., Thanos, D., and Aggarwal, A. K. (1998) Structure of IRF-1 with bound DNA reveals determinants of interferon regulation. Nature 391, 103–106.
Furui, J., Uegaki, K., Yamazaki, T., Shirakawa, M., Swindells, M. B., Harada, H., Taniguchi, T. and Kyogoku, Y. (1998) Solution structure of the IRF-2 DNA-binding domain: a novel subgroup of the winged helix-turn-helix family. Structure 6, 491–500.
Kirchhoff, S., Schaper, F., Oumard, A., and Hauser, H. (1998) In vivo formation of IRF-1 homodimers. Biochimie 80, 659–664.
Burysek, L., Yeow, W. S., and Pitha, P. M. (1999) Unique properties of a second human herpesvirus 8-encoded interferon regulatory factor (vIRF-2). J. Hum. Virol. 2, 19–32.
Masumi, A., Wang, I.-M., Lefebvre, B., Yang, X.-J., Nakatani, Y., and Ozato, K. (1999) The histone acetylase PCAF is a phorbol-esterinducible coactivator of the IRF family that confers enhanced interferon responsiveness. Mol. Cell. Biol. 19, 1810–1820.
Meraro, D., Hashmueli, S., Koren, B., Azriel, A., Oumard, A., Kirchhoff, S., Hauser, H., Nagulapalli, S., Atchison, M. L., and Levi, B.-Z., (1999) Protein-protein and DNA-protein interactions affect the activity of lymphoid-specific IRFs. J. Immunol. 163, 6468–6478.
Nelson, N., Marks, M. S., Driggers, P. H., and Ozato, K. (1993) Interferon Consensus Sequence-Binding Protein, a member of the Interferon Regulatory Factor family, suppresses interferon-induced gene transcription. Mol. Cell. Biol. 13, 588–599.
Li, W., Nagineni, C. N., Ge, H., Efiok, B., Chepelinski, A. B., and Egwuagu, C. E. (1999) Interferon consensus sequence-binding protein is constitutively expressed and differentially regulated in the ocular lens. J. Biol. Chem. 274, 9686–9691.
Li, W., Nagineni, C. N., Hooks, J. J., Cheplinski, A. B., and Egwuagu, C. E. (1999) IFNγ signaling in human retinal pigment epithelial cells mediated STAT1, ICSBP and IRF-1 transcription factors, Invest. Ophthalmol. Vis. Sci. 40, 976–982.
Politis, A. D., Sivo, J., Driggers, P. H., Ozato, K., and Vogel, S. N. (1992) Modulation of interferon consensus sequence binding protein mRNA in murine peritoneal macrophages: induction by IFN γ and down-regulation by IFN α/β, dexamethasone, and protein kinase inhibitors. J. Immunol. 1992, 801–807.
Politis, A. D., Ozato, K., Coligan, J. E., and Vogel, S. N. (1994) Regulation of IFN—induced nuclear expression of IFN consensus sequence binding protein in murine peritoneal macrophages. J. Immunol. 152, 2270–2278.
Weisz, A., Kirchhoff, S., and Levi, B.-Z. (1994) IFN consensus sequence binding protein (ICSBP) is a conditional repressor of IFN inducible promoters. International Immunol. 6, 1125–1131.
Weisz, A., Marx, P., Sharf, R., Appella, E., Driggers, P. H., Ozato, K., and Levi, B.-Z. (1992) Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes. J. Biol. Chem. 267, 25589–25596.
Kantakamalakul, W., Politis, A. D., Marecki, S., Sullivan, T., Ozato, K., Fenton, M. J., and Vogel, S. N. (1999) Regulation of Interferon Consensus Sequence Binding Protein (ICSBP) Expression in murine macrophages. J. Immunol. 162, 7417–7425.
Marecki, S., Atchison, M. L., and Fenton, M. J. (1999) Differential expression and distinct functions of Interferon Regulatory Factor 4 (IRF4) and Interferon Consensus Sequence Binding Protein (ICSBP) in macrophages. J. Immunol. 163, 2713–2722.
Kim, Y.-M., Kang, H.-S., Paik, S.-G., Pyun, K.-H., Anderson, K. L., Torbett, B. E., and Choi, I. (1999) Roles of IFN Consensus Sequence Binding Protein and PU.1 in regulating IL-18 gene expression. J. Immunol. 163, 2000–2007.
Holtschke, T., Lohler, J., Kanno, Y., Fehr, T., Giese, N., Rosenbauer, F., Lou, J., Knobeloch, K.-P., Gabriele, L., Waring, J., Bachmann, M. F., Zinkernagel, R. M., Morse III, H. C., Ozato, K., and Horak, I. (1996) Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell 87, 307–317.
Scharton-Kersten, T., Contursi, C., Masumi, A., Sher, A., and Ozato, K. (1997) Interferon Consensus Sequence Binding Protein-deficient mice display impaired resistance to intracellular infection due to a primary defect in interleukin 12 p40 induction. J. Exp. Med. 186, 1523–1534.
Giese, N. A., Gabriele, L., Doherty, T. M., Klinman, D. M., L., T.-H., Contursi, C., Epstein, S. L., and Morse III. H. C. (1997) Interferon (IFN) Consensus Sequence-binding Protein, a transcription factor of the IFN Regulatory Factor family, regulates immune responses in vivo through control of interleukin 12 production. J. Exp. Med. 186 1535–1546.
Contursi, C., Wang, I.-M., Gabriele, L., Gadina, M., O'Shea, J., Morse III. H. C., and Ozato, K. (2000) IFN consensus sequence binding protein potentiates STAT-1-dependent activation of IFNγ-responsive promoters in macrophages. PNAS 97, 91–96.
Schmidt, M., Nagel, S., Proba, J., Thiede, C., Ritter, M., Waring, J. F., Rosenbauer, F., Huhn, D., Horak, W. B., I., and N. A. (1998) Lack of interferon consesus sequence binding protein (ICSBP) transcripts in human myeloid leukemias. Blood 91, 22–29.
Hao, S. X., and Ren, R. (2000) Expression of interferon consensus sequence binding protein (ICSBP) is downregulated in Bcr-Abl-induced murine chronic myelogenous leukemia-like disease, and forced coexpression of ICSBP inhibits Bcr-Abl-induced myeloproliferative disorder. Mol. Cell. Biol. 20, 1149–1161.
Grossman, A., Mittrucker, H. W., Nicholl, J., Suzuki, A., Chung, S., Antonio, L., Suggs, S., Sutherland, G. R., Siderovski, D. P., and Mak, T. W. (1996) Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25. Genomics 37, 229–233.
Brass, A. L., Kehrli, E., Eisenbeis, C. F., Storb, U., and Sing, H. (1996) Pip, a lymphoidrestricted IRF, contains a regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor PU. 1. Genes Dev. 10, 2335–2347.
Grumont, R. J., and Gerondakis, S. (2000) Rel induces interferon regulatory factor 4 (IRF-4) expression in lymphocytes: modulation of interferon-regulated gene expression by rel/nuclear factor κB. J. Exp. Med. 191, 1281–1291.
Mittrucker, H.-W., Matsuyama, T., Grossman, A., Kundig, T. M., Potter, J., Shahinian, A., Wakeham, A., Patterson, B., Ohashi, P. S., and Mak, T. W. (1997) Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function. Science 275, 540–543.
Iida, S., Rao, P. H., Butler, M., Corradini, P., Boccadoro, M., Klein, B., Chaganti, R. S. K., and Dalla-Favera, R. (1997) Deregulation of MUMI/IRF4 by chromosomal translocation in multiple myeloma. Nature Genetics 17, 226–230.
Strauss-Soukup, J. K., and Maher, L. J. I. (1997) Role of asymetric phosphate neutralization in DNA bending by PU. 1. J. Biol. Chem. 272, 31570–31575.
Wang, Y. H., and Griffith, J. D. (1996) The [(G/C)3NN]n motif: a common DNA repeat that excludes nucleosomes. PNAS 93, 8863–8867.
Nikolajczyk, B. S., Sanchez, J. A., and Sen, R. (1999) ETS protein-dependent accessibility changes at the immunoglobulin mu heavy chain enhancer. Immunity 11, 11–20.
Bovelenta, C., Driggers, P. H., Marks, M. S., Medin, J. A., Politis, A. D., Vogel, S. N., Levy, D. E., Sakaguchi, K., Appella, E., Coligan, J. E., and Ozato, K. (1994) Molecular interaction between interferon consensus sequence binding protein and members of the interferon regulatory factor family. PNAS 91, 5046–5050.
Sharf, R., Meraro, D., Azriel, A., Thornton, A. M., Ozato, K., Petricoin, E. F., Larner, A. C., Schaper, F., Hauser, H., and Levi, B.-Z. (1997). Phosphorylation events modulate the ability of Interferon Consensus Sequence Binding Protein to interact with Interferon Regulatory factors and bind to DNA. J. Biol. Chem. 272, 9785–9792.
Sharf, R., Azriel, A., Lijbkowicz, F., Winigrad, S. S., Ehrlich, R., and L. B. Z. (1995) Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors. J. Biol. Chem. 270, 1306–13069.
Schafer, S. L., Lin, R., Moore, P. A., Hiscott, J., and Pitha, P. M. (1998) Regulation of type I interferon gene expression by interferon regulatory factor 3. J. Biol. Chem. 273, 2714–2720.
Rao, S., Matsumura, A., Yoon, J., and Simon, M. C. (1999) Spi-B activates transcription via a unique proline, serine, and threonine domain and exhibits DNA binding affinity differences from PU.1. J. Biol. Chem. 274, 11115–111124.
Lodie, T. A., Reiner, M., Coniglio, S., Viglianti, G., and Fenton, M. J. (1998) Both PU.1 and Nuclear Factor κB mediate lipopolysaccharide-induced HIV-1 long terminal repeat transcription in macrophages. J. Immunol. 161, 268–276.
Lau, J. F., Parisien, J. P., and Horvath, C. M. (2000) Interferon regulatory factor subcellular localization is determined by a bipartite nuclear localization signal in the DNA-binding domain and interaction with cytoplasmic retention factors. PNAS 97, 7278–7283.
Takaoka, A., Tanaka, N., Mitani, Y., Miyazaki, T., Fujii, H., Sato, M., Kovarik, P., Decker, T., Schlessinger, J., and Taniguchi, T. (1999) Protein tyrosine kinase Pyκ2 mediates the Jak-dependent activation of MAPK and Statl in IFN-gamma, but not IFN-alpha signalling. EMBO J. 18, 2480–2488.
Gupta, S., Xia, D., Jiang, M., Lee, S. and Pernis, A. B. (1998) Signalling pathways mediated by the TNF- and cytokine-receptor families target a common cis-element of the IFN regulatory factor 1 promoter. J. Immunol. 161, 5997–6004.
Lin, R., and Hiscott, J. (1999) A role for casein kinase II phosphorylation in the regulation of IRF-1 transcriptional activity. Mol. Cell. Biol. 191, 169–180.
Birnbaum, M. J., van Zundert, B., Vaughn, P. S., Whitmarsh, A. J., van Wijnen, A. J., Davis, R. J., Stein, G. S., and Stein, J. L. (1997) Phosphorylation of the oncogenic transcription factor interferon regulatory factor 2 (IRF2) in vitro and in vivo. J. Cell. Biochem. 66, 175–183.
Perkel, J. M., and Atchison, M. L. (1998) A twostep mechanism for recruitment of Pip by PU. 1. J. Immunol. 160, 241–252.
Brass, A. L., Zhu, A. Q., and Singh, H. (1999) Assembly requirements of PU. 1-Pip (IRF4) activator complexes: inhibiting function in vivo using fused dimers. EMBO 18, 977–991.
Oritz, M. A., Light, J., Maki, R. A., and Assa-Munt, N. (1999) Mutation analysis of the Pip interaction domain reveal critical residues for protein-protein interactions. PNAS 96, 2740–2745.
Yee, A. A., Yin, P., Siderovski, D. P., Mak, T. W., Litchfield, D. W., and Arrowsmith, C. H. (1998) Cooperative interaction between the DNA-binding domains of PU.1 and IRF4. J. Mol. Biol. 279, 1075–1083.
Gross, P., Yee, A. A., Arrowsmith, C. H., and Macgregor, J. R. B. (1998) Quantitative hydroxyl radical footprinting reveals cooperative interactions between DNA-binding subdomains of PU.1 and IRF4. Biochemistry 37, 9802–9811.
Marecki, S., Riendeau, C. J., and Fenton, M. J. (2000) PU.1 and multiple IRF family members dramatically synergize to drive expression of the IL-1β gene via a distal enhancer. Submitted.
Tsukada, J., Waterman, W. R., Koyama, Y., Webb, A. C., and Auron, P. E. (1996) A novel STAT-like factor mediates lipopolysaccharide, interleukin 1 (il-1), and IL-6 signaling and recognizes a gamma interferon activation site-like element in the IL-1beta gene. Mol. Cell. Biol. 16, 2183–2194.
Ozato, K. (1998) The IRF family: its diverse roles in regulating gene expression by interferon/cytokine, in host defense, and cancer/apoptosis. In 2nd Joint Meeting, of the ICS and ISICR, Vol. 9, Eur. Cytokinw Netw., Jerusalem, p. 340.
Wang, I. M., Contursi, C., Masumi, A., Ma, X., Trinchieri, G., and Ozato, K. (2000) An IFN—inducible transcription factor IFN consensus sequence binding protein (ICSBP), stimulates IL-12 p40 expression in macrophages J. Immunol. 165, 271–279.
Cheng, G., Nazar, A. S. M. I., Shin, H. S., Vanguri, P., and Shin, M. L. (1998) IP-10 gene transcription by virus in astrocytes requires cooperation of ISRE with adjacent kB site but not IRF-1 or viral transcription. J. Interferon Cytokine Res. 18, 987–997.
Lin, R., Heylbroeck, C., Pitha, P. M., and Hiscott, J. (1998) Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation. Mol. Cell. Biol. 18, 2986–2996.
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Marecki, S., Fenton, M.J. PU.1/interferon regulatory factor interactions. Cell Biochem Biophys 33, 127–148 (2000). https://doi.org/10.1385/CBB:33:2:127
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DOI: https://doi.org/10.1385/CBB:33:2:127