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Pip, a lymphoid-restricted IRF, contains a regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor PU.1.
Open accessAbstract
Pip is a lymphoid-restricted IRF transcription factor that is recruited to composite elements within immunoglobulin light-chain gene enhancers through a specific interaction with the Ets factor PU.1. We have examined the transcriptional regulatory properties of Pip as well as the requirements for its interaction with PU.1 and DNA to form a ternary complex. We demonstrate that Pip is a dichotomous regulator; it specifically stimulates transcription in conjunction with PU.1, but represses alpha/beta-interferon-inducible transcription in the absence of PU.1. Thus, during B-cell activation and differentiation, Pip may function both as an activator to promote B cell-specific gene expression and as a repressor to inhibit the antiproliferative effects of alpha/beta-interferons. Mutational analysis of Pip reveals a carboxy-terminal segment that is important for autoinhibition of DNA binding and ternary complex formation. A domain of Pip containing this segment confers autoinhibition and PU.1-dependent binding activity to the DNA-binding domain of the related IRF family member, p48. On the basis of these and other data we propose a model for PU.1/Pip ternary complex formation.
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In the citing paper
“A C-terminal regulatory domain within Pip itself is also required for ternary complex assembly (Brass et al., 1996).”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Pip deletion mutants which retained the ability to form a ternary complex with PU.1 (1-439 and 1-419; Brass et al., 1996; data not shown) stimulated transcription comparable with full-length Pip.”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As shown previously, full-length Pip cannot bind to DNA in the absence of PU.1; however, a C-terminal deletion mutant, Pip 1-410, can bind DNA independently (Figure 2A, compare lanes 2 and 3; Brass et al.,1996).”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“we identified a predicted α-helix within Pip's C-terminus (amino acids 395-413) that is critical for both formation of a ternary complex and autoinhibition of DNA binding”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“it appears that other, as yet uncharacterized helices within this region may pack together with Pip's helix amino acids 395-413 to form a tertiary fold which is competent for PU.1 association.”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Similar protein-protein interaction between PU.1 and PIP has been detected in the Ig λ light chain enhancer and the CD20 promoter (27-29”
From AKT Induces Transcriptional Activity of PU.1 through Phosphorylation-mediated Modifications within Its Transactivation Domain (2001) · cites this paper as [27]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In addition, this regulatory domain autoinhibits binding of Pip to DNA in the absence of PU.1.”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
The cited source says what the claim attributes to it.
In the citing paper
“Therefore, this domain contains structural determinants important for both PU.1 interaction and autoinhibition (Brass et al., 1996).”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
The cited source says what the claim attributes to it.
In the citing paper
“Previously, using deletion analysis and secondary structure predictions, we suggested that a putative α-helical region (amino acids 399-413) in Pip's C-terminus is important for ternary complex formation with PU.1 (Figure 1A and B; Brass et al., 1996).”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
The cited source says what the claim attributes to it.
In the citing paper
“PU.1 and Pip represent the major components of the ternary complex formed with nuclear extract from these cells”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
The cited source says what the claim attributes to it.
In the citing paper
“This is consistent with increased expression of Pip in plasma cell lines such as J558L”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
The cited source says what the claim attributes to it.
In the citing paper
“PIP is expressed exclusively in the lymphoid lineages (27”
From AKT Induces Transcriptional Activity of PU.1 through Phosphorylation-mediated Modifications within Its Transactivation Domain (2001) · cites this paper as [27]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Probes B1 and C1 differ in their flanking sequences”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Brass et al., 1996
Experimental — accuracy not yet measuredIn the citing paper
“Pip/NF-EM5/IRF-4, a member of IRF family, is a lymphoid-restricted transcription factor that is recruited to a composite element (IRF/ETS-binding site) within Ig light chain enhancers through a specific interaction with PU.1 protein [116, 117].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [117]
In the citing paper
“In the second step, phosphorylation of PU.1 at Ser 148 results in a conformational change in Pip (either before or after interaction with Pip) allowing cooperative DNA binding [117].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [117]
In the citing paper
“Analogous to the PU.1-Pip interaction, the PU.1-ICSBP interaction is DNA directed and facilitated by EICE (4, 38).”
From Gamma Interferon Triggers Interaction between ICSBP (IRF-8) and TEL, Recruiting the Histone Deacetylase HDAC3 to the Interferon-Responsive Element (2002) · cites this paper as [4]
In the citing paper
“Although the majority of IRF family members are expressed broadly in many cell types, ICSBP and another member, Pip (IRF-4), are expressed only in the immune system (4, 12, 49).”
From Gamma Interferon Triggers Interaction between ICSBP (IRF-8) and TEL, Recruiting the Histone Deacetylase HDAC3 to the Interferon-Responsive Element (2002) · cites this paper as [4]
In the citing paper
“The PU.1ICSBP complex and the PU.1-Pip complex are shown to act as a stimulators of EICE-mediated transcription (4, 40).”
From Gamma Interferon Triggers Interaction between ICSBP (IRF-8) and TEL, Recruiting the Histone Deacetylase HDAC3 to the Interferon-Responsive Element (2002) · cites this paper as [4]
In the citing paper
“ICSBP has been known to interact with PU.1, a hematopoietic-cellspecific member of the Ets family (4, 5, 38).”
From Gamma Interferon Triggers Interaction between ICSBP (IRF-8) and TEL, Recruiting the Histone Deacetylase HDAC3 to the Interferon-Responsive Element (2002) · cites this paper as [4]
In the citing paper
“IRF-4 is similar to ICSBP in structure, interacts with some common partners (PU.1 and E47), and regulates an overlapping set of target promoters. (31,32,63,64)”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [64]
In the citing paper
“IRF-4 is similar to ICSBP in structure, interacts with some common partners (PU.1 and E47), and regulates an overlapping set of target promoters. (31,32,63,64)”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [64]
In the citing paper
“IRF-4 is similar to ICSBP in structure, interacts with some common partners (PU.1 and E47), and regulates an overlapping set of target promoters. (31,32,63,64)”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [64]
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“1 to generate a unique B-cell-specific heterodimer (4, 7) IRF-3 was also shown previously to associate with IRF-7, and this heteromeric association may cooperatively activate the transcription from the IFN-b promoter (33).”
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Wang, I.-M., Contursi, C., Masumi, A., Ma, X., Trinchieri, G., & Ozato, K. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.1.271 · Cited by 187
“However, the fact that ICSBP has both positive and negative transcriptional activities may not be surprising, because other IRF members that repress ISRE-mediated transcription, such as IRF-2 and Pip/IRF-4, are shown to be capable of enhancing transcription from other promoters (50, 51).”
BackgroundReview: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells
Tamura, T., & Ozato, K. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452755 · Cited by 183
Analysis of MUM1/IRF4 Protein Expression Using Tissue Microarrays and Immunohistochemistry
Natkunam, Y., Warnke, R. A., Montgomery, K. D., Falini, B., & van de Rijn, M. (2001) · Modern Pathology · doi:10.1038/modpathol.3880373 · Cited by 176
Eklund, E. A., Jalava, A., & Kakar, R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13957 · Cited by 176
Transcription Factors in Lymphocyte Development— T and B Cells Get Together
Glimcher, L. H., & Singh, H. (1999) · Cell · doi:10.1016/s0092-8674(00)80955-1 · Cited by 157
Self-citationTranscriptional regulation of follicular T‐helper (Tfh) cells
Liu, X., Nurieva, R., & Dong, C. (2013) · Immunological Reviews · doi:10.1111/imr.12040 · Cited by 161
“IRF4, a weak DNA binder due to its C-terminal auto-inhibitory domain, is restricted to immune cells in its expression (33, 35).”
BackgroundCrystal structure of PU. 1/IRF-4/DNA ternary complex
Escalante, C. R., Brass, A. L., Pongubala, J. M. R., Shatova, E., Shen, L., Singh, H., & Aggarwal, A. K. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00703-7 · Cited by 154
Self-citationPhosphorylation represses Ets-1 DNA binding by reinforcing autoinhibition
Cowley, D. O., & Graves, B. J. (2000) · Genes & Development · doi:10.1101/gad.14.3.366 · Cited by 152
“Examples of this phenomenon include cooperative binding partnerships between a1 and a2 (Stark et al. 1999), PU.1 and Pip (Brass et al. 1996), Elk-1 or Sap-1 and SRF (Dalton and Treisman 1992; Ling et al. 1997), and others.”
BackgroundGu, T.-L., Goetz, T. L., Graves, B. J., & Speck, N. A. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.1.91-103.2000 · Cited by 150
“2C), and CBFa2(1-214) and CBFa2(41-214) displayed only a twofold difference in affinity (Fig.”
BackgroundMethodInfluentialInterferon regulatory factor family of transcription factors and regulation of oncogenesis
Takaoka, A., Tamura, T., & Taniguchi, T. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2007.00720.x · Cited by 152
Meraro, D., Hashmueli, S., Koren, B., Azriel, A., Oumard, A., Kirchhoff, S., Hauser, H., Nagulapalli, S., Atchison, M. L., & Levi, B.-Z. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.12.6468 · Cited by 147
Marié, I., Smith, E., Prakash, A., & Levy, D. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.23.8803-8814.2000 · Cited by 161
“Therefore, while phosphorylation of IRF3 appears to mask its nuclear export signal, leading to its accumulation in the nucleus, phosphorylation of IRF7 either occurs only in the nucleus or modulates subcellular localization by a distinct mechanism.”
BackgroundInfluentialIRF8 regulates B-cell lineage specification, commitment, and differentiation
Wang, H., Lee, C. H., Qi, C., Tailor, P. B., Feng, J., Abbasi, S., Atsumi, T., & Morse, H. C. (2008) · Blood · doi:10.1182/blood-2008-01-129049 · Cited by 144
The diverse roles of IRF4 in late germinal center B‐cell differentiation
Silva, N. S. D., Simonetti, G., Heise, N., & Klein, U. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01113.x · Cited by 154
“1 is able to unmask the DBD of IRF4 (2, 39), thus facilitating its recruitment to the enhancer loci.”
BackgroundMolecular mechanisms of ETS transcription factor-mediated tumorigenesis
Kar, A., & Gutierrez‐Hartmann, A. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.838202 · Cited by 151
“Covalently tethered PU.1–Pip chimeras regulate the expression of different genes to PU.1 alone (Brass et al., 1996).”
BackgroundWhen Ets transcription factors meet their partners
Verger, A., & Duterque‐Coquillaud, M. (2002) · BioEssays · doi:10.1002/bies.10068 · Cited by 134
Monocyte differentiation and macrophage polarization
Orekhov, A. N., Orekhova, V. A., Nikiforov, N. G., Myasoedova, V. A., Grechko, A. V., Romanenko, E. B., Zhang, D., & Chistiakov, D. A. (2019) · Vessel Plus · doi:10.20517/2574-1209.2019.04 · Cited by 144
“Among the pro-inflammatory genes induced by IRF-8 are IL-12p40, IL-12p35, IFN-β, and iNOS, that are characteristic for the M1 macrophage phenotype[55].”
BackgroundInfluentialIRF5:RelA Interaction Targets Inflammatory Genes in Macrophages
Saliba, D. G., Heger, A., Eames, H. L., Oikonomopoulos, S., Teixeira, A. S., Blazek, K. D., Androulidaki, A., Wong, D., Goh, F. G., Weiss, M., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.034 · Cited by 133
“This site was previously reported for immune cell developmentrelated IRF4 and IRF8 (Brass et al., 1996; Escalante et al., 2002; Tamura et al., 2005).”
BackgroundAuto-Inhibition of Ets-1 Is Counteracted by DNA Binding Cooperativity with Core-Binding Factor α2
Goetz, T. L., Gu, T.-L., Speck, N. A., & Graves, B. J. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.1.81-90.2000 · Cited by 128
“1 (9), and Pbx activates the DNA binding of its partner protein Hoxb (10, 11).”
BackgroundHuman and Mouse Mononuclear Phagocyte Networks: A Tale of Two Species?
Reynolds, G., & Haniffa, M. A. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00330 · Cited by 138
“1 interacts with Irf4 but also upregulates Flt3 expression critical for early DC differentiation in mice (110, 111).”
BackgroundIdentification of target genes and a unique cis element regulated by IRF-8 in developing macrophages
Tamura, T., Thotakura, P., Tanaka, T. S., Ko, M. S. H., & Ozato, K. (2005) · Blood · doi:10.1182/blood-2005-01-0080 · Cited by 135
Lineage-Specific Modulation of Interleukin 4 Signaling by Interferon Regulatory Factor 4
Gupta, S. K., Jiang, M., Anthony, A., & Pernis, A. B. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.12.1837 · Cited by 132
Mudter, J., Amoussina, L., Schenk, M., Yu, J., Brüstle, A., Weigmann, B., Atreya, R. N., Wirtz, S. J., Becker, C., Hoffman, A. W., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33227 · Cited by 130
“IRF4 is a lymphoid-and myeloid-restricted member of the IRF family of transcription factors that binds to IFN sequence response elements present within the promoters of IRF-regulated genes (15, 18, 21).”
Immune cell-specific amplification of interferon signaling by the IRF-4/8-PU. 1 complex
Kanno, Y., Levi, B.-Z., Tamura, T., & Ozato, K. (2005) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2005.25.770 · Cited by 128
“45 The EICE was originally found in the immunoglobulin (cid:4) light chain gene enhancer.”
Masumi, A., Wang, I.-M., Lefebvre, B., Yang, X.-J., Nakatani, Y., & Ozato, K. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.1810 · Cited by 124
“1, a member of the ETS family, and this interaction allows them to bind to the immunoglobulin light-chain enhancer lB (10, 20).”
BackgroundIRF8 regulates myeloid and B lymphoid lineage diversification
Wang, H., & Morse, H. C. (2008) · Immunologic Research · doi:10.1007/s12026-008-8055-8 · Cited by 121
“IRF8 functions as a transcriptional activator or repressor depending on the formation of diVerent heterodimeric DNA binding complexes with partners that include members of ETS family (PU.1, TEL) [9, 10] and IRF family (IRF1, IRF2, and IRF4) [11–13] as well as E47 [14], NFATc1 [15], and MIZ1 [16].”
Luchin, A. I., Suchting, S., Merson, T. D., Rosol, T. J., Hume, D. A., Cassady, A. I., & Ostrowski, M. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106418200 · Cited by 124
Complex interactions of transcription factors in mediating cytokine biology in T cells
Li, P., Spolski, R. J., Liao, W., & Leonard, W. J. (2014) · Immunological Reviews · doi:10.1111/imr.12199 · Cited by 124
“1, or the closely related ETS family protein, SPIB, can relieve this auto-inhibition and increase binding affinity, allowing IRF4 to recognize composite ETS–IRF consensus motif elements (EICEs) (50-GGAAnnGAAA-30) (125, 127), and regulate a range of genes, including those encoding the j and k immunoglobulin light chain…”
BackgroundMa, S., Pathak, S., Trinh, L. X., & Lu, R. (2007) · Blood · doi:10.1182/blood-2007-08-110106 · Cited by 117
Modulation of T Cell Cytokine Production by Interferon Regulatory Factor-4
Hu, C.-M., Jang, S. Y., Fanzo, J., & Pernis, A. B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205895200 · Cited by 113
Marecki, S., Riendeau, C. J., Liang, M. D., & Fenton, M. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.11.6829 · Cited by 111
Interferon regulatory factor 4 and 8 in B-cell development
Lu, R. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.07.006 · Cited by 111
“1 or Spi-B and bind to the Ets-IRF composite element (EICE; GGAAnnGAAA) located in immunoglobulin (Ig) light chain κ 3’ (Ek3’) and λ gene enhancer regions [2-4].”
BackgroundInfluentialNathanson, J. L. (2009) · Frontiers in Neural Circuits · doi:10.3389/neuro.04.019.2009 · Cited by 111
“Synergistic interactions can be a result of cooperative binding (Moreno et al., 1995; Brass et al., 1996; Butscher et al., 1998; Muhlethaler-Mottet et al., 1998; Okuno et al., 2001) or hierarchical loading (Linhoff et al., 1997).”
Oikawa, T., Yamada, T., Kihara-Negishi, F., Yamamoto, H., Kondoh, N., Hitomi, Y., & Hashimoto, Y. (1999) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4400534 · Cited by 109
Transcriptional Control of Dendritic Cell Development
MURPHY, K. M. M. (2013) · Advances in immunology · doi:10.1016/b978-0-12-417028-5.00009-0 · Cited by 108
Roles of IFN Consensus Sequence Binding Protein and PU.1 in Regulating IL-18 Gene Expression
Kim, Y.-M., Kang, H.-S., Paik, S., Pyun, K.-H., Anderson, K. L., Torbett, B. E., & Choi, I. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.4.2000 · Cited by 103
“In addition, several studies (30, 36, 37) reported that PU.”
BackgroundZhao, B., & Sample, C. E. (2000) · Journal of Virology · doi:10.1128/jvi.74.11.5151-5160.2000 · Cited by 107
“GST fusion proteins that contained full-length Spi-1 (GST-Spi-1), the amino-terminal activation domain [GST-Spi-1 N (1-90)], or the C-terminal ets domain of either Spi-1 [GST-Spi-1 ets (90-264)] or Spi-B [GST-Spi-B ets (121-262)] were generated.”
BackgroundRaczkowski, F., Ritter, J., Heesch, K., Schumacher, V., Guralnik, A., Höcker, L., Raifer, H., Klein, M., Bopp, T., Harb, H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309378110 · Cited by 98
Posttranslational Regulation of IRF-4 Activity by the Immunophilin FKBP52
Mamane, Y., Sharma, S., Petropoulos, L., Lin, R., & Hiscott, J. B. (2000) · Immunity · doi:10.1016/s1074-7613(00)80166-1 · Cited by 95
IFN Regulatory Factor 4 and 8 Promote Ig Light Chain κ Locus Activation in Pre-B Cell Development
Ma, S., Turetsky, A., Trinh, L. X., & Lu, R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.11.7898 · Cited by 95
“1 or its close relative Spi-B, to regulate the activities of Ig 3 enhancer and enhancers (16, 17).”
BackgroundRole of Interferon Regulatory Factor 4 in the Regulation of Pathological Cardiac Hypertrophy
Jiang, D., Bian, Z., Zhang, Y., Zhang, S.-M., Liu, Y., Zhang, R., Chen, Y., Yang, Q., Zhang, X.-D., Fan, G., et al. (2013) · Hypertension · doi:10.1161/hypertensionaha.111.00614 · Cited by 92
“In immune cell system, it has been reported that IRF4 functions as a positive regulator of many downstream transcription factors (ie, NFAT, signal transducer and activator of transcription 3 [STAT3/6], and forkhead box P3 [FOXP3]) by interacting with its C-terminal transactivation domain.(19) However, IRF4-controlled…”
BackgroundNF-IL6 (C/EBPβ) Vigorously Activates il1b Gene Expression via a Spi-1 (PU.1) Protein-Protein Tether
Yang, Z., Wara-aswapati, N., Chen, C., Tsukada, J., & Auron, P. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000145200 · Cited by 92
Guria, S., Hoory, A., Das, S., Chattopadhyay, D., & Mukherjee, S. (2023) · Bioscience Reports · doi:10.1042/bsr20220200 · Cited by 105
Marecki, S., Atchison, M. L., & Fenton, M. J. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.5.2713 · Cited by 87
Himmelmann, A., Riva, A., Wilson, G. L., Lucas, B. P., Thevenin, C., & Kehrl, J. H. (1997) · Blood · doi:10.1182/blood.v90.10.3984 · Cited by 68
Wang, H., Jain, S., Li, P., Lin, J.-X., Oh, J., Qi, C., Gao, Y., Sun, J., Sakai, T., Naghashfar, Z., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901258116 · Cited by 81
IRF4 and its regulators: evolving insights into the pathogenesis of inflammatory arthritis?
Biswas, P. S., Bhagat, G., & Pernis, A. B. (2009) · Immunological Reviews · doi:10.1111/j.0105-2896.2009.00864.x · Cited by 84
Little, H., Rorick, N. K., Su, L.-I., Baldock, C., Malhotra, S., Jowitt, T., Gakhar, L., Ramaswamy, S., Schutte, B. C., Dixon, M. J., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn381 · Cited by 80
Gupta, P., Gurudutta, G. U., Saluja, D., & Tripathi, R. P. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00757.x · Cited by 74
“1 at Ser 148 results in a conformational change in Pip (either before or after interaction with Pip) allowing cooperative DNA binding [117].”
BackgroundGualco, G., Weiss, L. M., & Bacchi, C. E. (2010) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0b013e3181cf1126 · Cited by 80
“MUM1/IRF4 protein plays a positive regulator role in transcription, using its C-terminal transactivation domain.(27) Although the exact physiologic function is still obscure, MUM1/ IRF4 cooperates with PU.”
BackgroundA Two-Step Mechanism for Recruitment of Pip by PU.1
Perkel, J. M., & Atchison, M. L. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.1.241 · Cited by 77
“The DNA-binding domain of Pip is designated DBD, and the autoinhibitory domain (30) is indicated by a shaded region.”
BackgroundInfluentialPU.1/Interferon Regulatory Factor Interactions; Mechanisms of Transcriptional Regulation
Marecki, S., & Fenton, M. J. (2000) · Cell Biochemistry and Biophysics · doi:10.1385/cbb:33:2:127 · Cited by 74
IRF4 in multiple myeloma—Biology, disease and therapeutic target
Agnarelli, A., Chevassut, T. J. T., & Mancini, E. J. (2018) · Leukemia Research · doi:10.1016/j.leukres.2018.07.025 · Cited by 75
Transcriptional regulation of B-cell differentiation
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Metadata
- Authors
- Brass, A. L., Kehrli, E., Eisenbeis, C. F., Storb, U., & Singh, H.
- Affiliations
- Howard Hughes Medical Institute (US)
- ORCID
- Singh, H
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1996-09-15
- Volume
- 10
- Issue
- 18
- Pages
- 2335-2347
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2005606581
- Cited by
- 242
- References
- 49
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 15 · 2012: 11
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- York University
- National Institutes of Health
- U.S. Public Health Service (FM07183)
- National Institute of General Medical Sciences (T32GM007281, GM-07281)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-07009)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- Pip, interferon regulatory factors, PU.1, ETS transcription factors, ternary complex formation, autoinhibition, B cell activation, transcriptional repression, p48, DNA-binding domain
- MeSH terms
- Interferon Regulatory Factor-8, Interferon Regulatory Factor-4, Proto-Oncogene Protein Spi-1, Animals, B-Lymphocytes, Binding Sites, Carrier Proteins, DNA-Binding Proteins, Gene Expression Regulation, Interferon-gamma, Models, Molecular, Nucleic Acid Conformation, Protein Conformation, Proto-Oncogene Proteins, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Transcription Factors, Transcription, Genetic, Trans-Activators, Interferon-alpha, Interferon-Stimulated Gene Factor 3, Interferon-Stimulated Gene Factor 3, gamma Subunit, Interferon Regulatory Factors, Mice
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