The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
“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 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 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]
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]
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Recombinant Genomes Which Express Chloramphenicol Acetyltransferase in Mammalian Cells
Gorman, C., Moffat, L. F., & Howard, B. H. (1982) · Molecular and Cellular Biology · doi:10.1128/mcb.2.9.1044 · Cited by 7,674
Site-directed mutagenesis by overlap extension using the polymerase chain reaction
Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K., & Pease, L. R. (1989) · Gene · doi:10.1016/0378-1119(89)90358-2 · Cited by 7,414
Garnier, J., Osguthorpe, D. J., & Robson, B. (1978) · Journal of Molecular Biology · doi:10.1016/0022-2836(78)90297-8 · Cited by 4,523
TRANSCRIPTIONAL RESPONSES TO POLYPEPTIDE LIGANDS: The JAK-STAT Pathway
Schindler, C., & Darnell, J. E. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.003201 · Cited by 1,808
Regulation of Inducible and Tissue-Specific Gene Expression
Maniatis, T., Goodbourn, S., & Fischer, J. A. (1987) · Science · doi:10.1126/science.3296191 · Cited by 1,553
Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages
Scott, E. W., Simon, M. C., Anastasi, J., & Singh, H. (1994) · Science · doi:10.1126/science.8079170 · Cited by 1,532
Self-citationHarada, H., Fujita, T., Miyamoto, M., Kimura, Y., Maruyama, M., Furia, A., Miyata, T., & Taniguchi, T. (1989) · Cell · doi:10.1016/0092-8674(89)90107-4 · Cited by 957
The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene
Klemsz, M. J., McKercher, S. R., Celada, A., Van Beveren, C., & Maki, R. A. (1990) · Cell · doi:10.1016/0092-8674(90)90219-5 · Cited by 954
Field, J. M., Nikawa, J., Broek, D., MACDONALD, B. S., Rodgers, L., Wilson, I. A., Lerner, R. A., & Wigler, M. H. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.5.2159 · Cited by 949
Beg, A. A., Ruben, S. M., Scheinman, R. I., Haskill, S., Rosen, C. A., & Baldwin, A. S. (1992) · Genes & Development · doi:10.17615/1ytj-h979 · Cited by 718
Flagged first, then by citations
Research works printed but not linked: 2
- 10.1101/gad.6.10.1899 · DOI
- McKnight, S. and Y. Yamamoto. 1992. Transcriptional regulation. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Cited by
Sorted by citations
Items 101–200 of 242
Rosenbauer, F., Waring, J. F., Foerster, J., Wietstruk, M., Philipp, D., & Horak, I. (1999) · Blood · doi:10.1182/blood.v94.12.4274 · Cited by 76
Transcription factors that regulate growth and differentiation of myeloid cells.
Nagamura-Inoue, T., Tamura, T., & Ozato, K. (2001) · International Reviews of Immunology · doi:10.3109/08830180109056724 · Cited by 94
Transcriptional control of B cell development and function
Bartholdy, B., & Matthias, P. (2003) · Gene · doi:10.1016/j.gene.2003.11.008 · Cited by 78
Pitha, P. M., Au, W. C., Lowther, W. J., Juang, Y.-T., Schafer, S. L., Burýšek, L., Hiscott, J. B., & Moore, P. A. (1998) · Biochimie · doi:10.1016/s0300-9084(99)80018-2 · Cited by 71
Lazzari, E., Korczeniewska, J., Gabhann, J. N., Smith, S., Barnes, B. J., & Jefferies, C. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103609 · Cited by 70
Review: ICSBP/IRF-8 Transactivation: A Tale of Protein-Protein Interaction
Levi, B.-Z., Hashmueli, S., Gleit-Kielmanowicz, M., Azriel, A., & Meraro, D. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452764 · Cited by 70
“(13,15) Cumulative results have revealed that the association of ICSBP and IRF-4 with other factors is a two-step mechanism.”
DNA Binding by the ETS Protein TEL (ETV6) Is Regulated by Autoinhibition and Self-association
Green, S. M., Coyne, H. J., McIntosh, L. P., & Graves, B. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.096958 · Cited by 69
PU.1 cooperates with IRF4 and IRF8 to suppress pre-B-cell leukemia
Pang, S. H. M., Minnich, M., Gangatirkar, P., Zheng, Z., Ebert, A., Song, G., Dickins, R. A., Corcoran, L. M., Mullighan, C. G., Busslinger, M., et al. (2016) · Leukemia · doi:10.1038/leu.2016.27 · Cited by 69
Bojović, B. B., & Hassell, J. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m005509200 · Cited by 68
Kuwata, T., Gongora, C., Kanno, Y., Sakaguchi, K., Tamura, T., Kanno, T., Basrur, V., Martinez, R., Appella, E., Golub, T., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.21.7439-7448.2002 · Cited by 69
“1, a hematopoietic-cellspecific member of the Ets family (4, 5, 38).”
BackgroundInfluentialNonkwelo, C., Ruf, I. K., & Sample, J. T. (1997) · Journal of Virology · doi:10.1128/jvi.71.9.6887-6897.1997 · Cited by 68
“1 (5, 57); however, because QRE-2 is not adjacent to a canonical GGAA element (an element present in Ets factor binding sites) and because IRF-4 cDNAs were not obtained in our one-hybrid screen, IRF-4 was not considered further.”
BackgroundRole of Transcription Factors C/EBPa and PU.1 in Normal Hematopoiesis and Leukemia
Koschmieder, S., Rosenbauer, F., Steidl, U., Owens, B. M., & Tenen, D. G. (2005) · International Journal of Hematology · doi:10.1532/ijh97.05051 · Cited by 72
“For example, IRF-4/Pip, a member of the interferon regulatory factor (IRF) family, which is expressed in lymphocytes and at lower levels in macrophages, synergizes with PU.1 to transactivate an element in the immunoglobulin light chain enhancers by forming a ternary complex with PU.1 on a composite IRF/ETS-binding sit…”
BackgroundCare, M. A., Cocco, M., Laye, J. P., Barnes, N., Huang, Y., Wang, M., Barrans, S., Du, M., Jack, A., Westhead, D. R., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku451 · Cited by 65
“TheDNAbinding domain of IRF4 is restricted via an autoinhibitory interaction (6), and release depends primarily on binding to transcription factor partners.”
BackgroundReview: The Role of IRF-4 in Transcriptional Regulation
Marecki, S., & Fenton, M. J. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452737 · Cited by 68
“(1,2,25,26) However, recent work from our laboratory and that of Rosenbauer et al. has demonstrated expression and function of IRF-4 in macrophages.”
Nagulapalli, S., & Atchison, M. L. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.8.4639 · Cited by 66
“This construct contains only the Pip DNA binding domain (7).”
BackgroundInfluentialGreenall, A., Willingham, N., Cheung, E., Boam, D. S., & Sharrocks, A. D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011582200 · Cited by 64
Disabled-2 is transcriptionally regulated by ICSBP and augments macrophage spreading and adhesion
Rosenbauer, F., Kallies, A., Scheller, M., Knobeloch, K., Rock, C. O., Schwieger, M., Stocking, C., & Horak, I. (2002) · The EMBO Journal · doi:10.1093/emboj/21.3.211 · Cited by 59
Xiong, H., Zhu, C. Y., Li, H., Chen, F., Mayer, L., Ozato, K., Unkeless, J. C., & Plevy, S. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209583200 · Cited by 64
IRF4 and IRF8: governing the virtues of B lymphocytes
Shukla, V., & Lu, R. (2014) · Frontiers in Biology · doi:10.1007/s11515-014-1318-y · Cited by 70
IRF8: Mechanism of Action and Health Implications
Moorman, H. R., Reategui-Almonacid, Y., Poschel, D. B., & Liu, K. (2022) · Cells · doi:10.3390/cells11172630 · Cited by 63
Wheat, W. H., Fitzsimmons, D., Lennox, H., Krautkramer, S. R., Gentile, L. N., McIntosh, L. P., & Hagman, J. R. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.2231 · Cited by 61
Review: The Role of IRF-4 in B and T Cell Activation and Differentiation
Pernis, A. B. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452728 · Cited by 63
“(34,39) The minimal IRF-4/Ets interaction domain has been delimited to a region containing two a -helical structures, which are highly conserved within the IRF family and may function as general interaction domains between IRF and their partners.”
Regulation of IFN Consensus Sequence Binding Protein Expression in Murine Macrophages
Kantakamalakul, W., Politis, A. D., Marecki, S., Sullivan, T., Ozato, K., Fenton, M. J., & Vogel, S. N. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.12.7417 · Cited by 61
Shah, P. C., Bertolino, E., & Singh, H. (1997) · The EMBO Journal · doi:10.1093/emboj/16.23.7105 · Cited by 61
“epitope-tagged proteins, Oct-2 or Oct-1 cDNAs were subcloned into pcDNA3-HA (Brass et al., 1996).”
BackgroundMethodInfluentialSelf-citationvan der Stoep, N., Quinten, E., Rezende, M. M., & van den Elsen, P. J. (2004) · Blood · doi:10.1182/blood-2004-03-0790 · Cited by 58
PU.1, a Shared Transcriptional Regulator of Lymphoid and Myeloid Cell Fates
SINGH, H., DEKOTER, R. P., & WALSH, J. C. (1999) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1999.64.13 · Cited by 66
Self-citationO’Reilly, D., Quinn, C. M., El‐Shanawany, T., Gordon, S., & Greaves, D. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212150200 · Cited by 56
Shin, D., Lee, C., & Morse, H. C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027384 · Cited by 59
Unlu, S., Kumar, A., Waterman, W. R., Tsukada, J., Wang, K. Z. Q., Galson, D. L., & Auron, P. E. (2007) · Molecular Immunology · doi:10.1016/j.molimm.2007.02.016 · Cited by 57
“This argues that a complex containing, in-part, a Spi-1•IRF association similar to that observed for the IgλL and 3′IgκL light-chain enhancers (Brass et al., 1996;Brass et al., 1999;Escalante et al., 2002;Perkel and Atchison, 1998) is important for activity.”
BackgroundMethodResultInfluentialTranscriptional Regulation of the Cyclooxygenase-2 Gene in Macrophages by PU.1
Joo, M., Park, G. Y., Wright, J. G., Blackwell, T. S., Atchison, M. L., & Christman, J. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306267200 · Cited by 56
The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors
Kwon, O. H., Lee, C., Lee, Y. I., Paik, S., & Lee, H. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.07.092 · Cited by 55
Rieske, P., & Pongubala, J. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007482200 · Cited by 54
Analysis of Gene Expression and Ig Transcription in PU.1/Spi-B-Deficient Progenitor B Cell Lines
Schweitzer, B. L., & DeKoter, R. P. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.1.144 · Cited by 51
Arguello, M., Sgarbanti, M., Hernandez, E., Mamane, Y., Sharma, S., Servant, M. J., Lin, R., & Hiscott, J. B. (2003) · Oncogene · doi:10.1038/sj.onc.1206270 · Cited by 52
“…0950-9232/03 $25.00 www.nature.com/onc molecular level, IRF-4 has a weak intrinsic DNA binding activity and its transactivation potential with respect to the Ets-IRF element depends on the formation of a complex with PU.1 (Pongubala et al., 1992; Eisenbeis et al., 1993, 1995; Brass et al., 1996).”
BackgroundInfluentialSchmidt, M., Bies, J., Tamura, T., Ozato, K., & Wolff, L. (2004) · Blood · doi:10.1182/blood-2003-01-0285 · Cited by 58
Schmidt, M., Hochhaus, A., König-Merediz, S. A., Brendel, C. A., Proba, J., Hoppe, G. J., Wittig, B., Ehninger, G., Hehlmann, R., & Neubauer, A. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.19.3331 · Cited by 51
Transcription factor networks in dendritic cell development
Satpathy, A. T., MURPHY, K. M. M., & Wumesh, K. C. (2011) · Seminars in Immunology · doi:10.1016/j.smim.2011.08.009 · Cited by 57
“In different settings, these interactions are critical in determining the DNA-binding specificity and functional nature of the IAD, either as an activator or repressor of transcription [91-93].”
BackgroundIRF8 is the target of SIRT1 for the inflammation response in macrophages
Jia, Y., Han, S., Li, J., Wang, H., Liu, J., Li, N., Yang, X., Shi, J., Han, J., Li, Y., et al. (2016) · Innate Immunity · doi:10.1177/1753425916683751 · Cited by 49
“Accumulated evidence suggests that acetylation of IRF family transcription factors is required for their optimal transcriptional activity.(28) Acetylation of diverse domains of IRF members results in a conformational change and thus influences their DNA-binding activities.”
BackgroundSpi‐B can functionally replace PU.1 in myeloid but not lymphoid development
Dahl, R. E., Ramírez‐Bergeron, D. L., Rao, S., & Simon, M. C. (2002) · The EMBO Journal · doi:10.1093/emboj/21.9.2220 · Cited by 48
Bathige, S. D. N. K., Whang, I., Umasuthan, N., Lim, B.-S., Park, M.-A., Kim, E., Park, H., & Lee, J. (2012) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2012.07.017 · Cited by 48
Rao, S., Matsumura, A., Yoon, J. W., & Simon, M. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.16.11115 · Cited by 46
Steroidogenic acute regulatory (StAR) protein: what's new?
Stocco, D. M. (1999) · BioEssays · doi:10.1002/(sici)1521-1878(199909)21:9 · Cited by 47
Transcriptional Control of Mature B Cell Fates
Wang, H., Morse, H. C., & Bolland, S. M. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.04.011 · Cited by 50
Sathish, N., Zhu, F. X., Golub, E. E., Liang, Q., & Yuan, Y. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.150920 · Cited by 46
Ortiz, M. A., Light, J. P., Maki, R. A., & Assa‐Munt, N. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.2740 · Cited by 44
van Dijk, T. B., Caldenhoven, E., Raaijmakers, J. A. M., Lammers, J.-W. J., Koenderman, L., & de Groot, R. P. (1998) · Blood · doi:10.1182/blood.v91.6.2126 · Cited by 43
Transcriptional control of metabolism by interferon regulatory factors
Ahmad, Z., Kahloan, W., & Rosen, E. D. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-00990-0 · Cited by 45
“IRF4 can bind as a homodimer to classic ISREs, and its functionality can expand by binding as a heterodimer with the transcription factor PU.1 to erythroblast transformation-specific IRF composite elements or with Fos–Jun proteins to activating protein 1 (AP1)–IRF composite elements (AICE1 or AICE2) 133–135 .”
Dendritic cell subsets and implications for cancer immunotherapy
Chen, M. Y., Zhang, F., Goedegebuure, S. P., & Gillanders, W. E. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1393451 · Cited by 44
Lee, J., Zhang, J., Chung, Y., Kim, J. H., Kook, C. M., González-Navajas, J. M., Herdman, D. S., Nürnberg, B., Insel, P. A., Corr, M., et al. (2020) · eLife · doi:10.7554/elife.49416 · Cited by 41
Activation and Regulation of Interferon Regulatory Factor 4 in HTLV Type 1-Infected T Lymphocytes
Sharma, S., Mamane, Y., Grandvaux, N., Bartlett, J., Petropoulos, L., Lin, R., & Hiscott, J. B. (2000) · AIDS Research and Human Retroviruses · doi:10.1089/08892220050193047 · Cited by 41
“9,25,26 As previously shown, IRF-4 alone did not bind to the l B element (Fig.”
Alter-Koltunoff, M., Ehrlich, S., Dror, N., Azriel, A., Eilers, M., Häuser, H., Bowen, H., Barton, C. H., Tamura, T., Ozato, K., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307954200 · Cited by 42
ETV7 limits antiviral gene expression and control of influenza viruses
Froggatt, H. M., Harding, A. T., Heaton, B. E., & Heaton, N. S. (2021) · Science Signaling · doi:10.1126/scisignal.abe1194 · Cited by 44
Sha, Y., & Markovic‐Plese, S. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00543 · Cited by 41
Cooperative Transcription Factor Complexes in Control
Martínez, G., & Rao, A. (2012) · Science · doi:10.1126/science.1231310 · Cited by 38
The interferon-inducible murine p48 (ISGF3γ) gene is regulated by protooncogene c- myc
Weihua, X., Lindner, D. J., & Kalvakolanu, D. V. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7227 · Cited by 39
Mechanisms of Interferon Action
Leaman, D. W. (1998) · Progress in molecular and subcellular biology · doi:10.1007/978-3-642-72149-6_6 · Cited by 39
Cooperative interaction between the DNA-binding domains of PU.1 and IRF4
Yee, A. A., Yin, P., Siderovski, D. P., Mak, T. W., Litchfield, D. W., & Arrowsmith, C. H. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1838 · Cited by 38
Fedele, P. L., Liao, Y., Gong, J., Yao, Y., van Delft, M. F., Low, M. S. Y., Tai, L., Herold, M. J., Jackson, J. T., Teh, C. E., et al. (2020) · Leukemia · doi:10.1038/s41375-020-01078-0 · Cited by 38
IRF4 as an Oncogenic Master Transcription Factor
Wong, R. W. J., Ong, J. Z. L., Theardy, M. S., & Sanda, T. (2022) · Cancers · doi:10.3390/cancers14174314 · Cited by 39
“1 dimer to bind to the EICE motif [12,33].”
BackgroundAutoinhibition as a Transcriptional Regulatory MechanismPreprint
Graves, B. J., Cowley, D. O., Goetz, T. L., Petersen, J. M., Jonsen, M. D., & Gillespie, M. E. (1998) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1998.63.621 · Cited by 35
Rosenbauer, F., Wagner, K., Zhang, P., Knobeloch, K., Iwama, A., & Tenen, D. G. (2004) · Blood · doi:10.1182/blood-2003-08-2688 · Cited by 35
Interferon Regulatory Factor 4 Contributes to Transformation of v-Rel-Expressing Fibroblasts
Hrdličková, R., Nehyba, J., & Bose, H. R. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.19.6369-6386.2001 · Cited by 35
“The C-terminal sequences may be conserved because of their ability to regulate the DNA binding of IRF-4 (13).”
BackgroundRepression of IRF-4 target genes in human T cell leukemia virus-1 infection
Mamane, Y., Grandvaux, N., Hernandez, E., Sharma, S., Innocente, S. A., Lee, J. M., Azimi, N., Lin, R., & Hiscott, J. B. (2002) · Oncogene · doi:10.1038/sj.onc.1205843 · Cited by 35
“These results are partially explained by the fact that probe 3 possesses two IRF binding sites and probe 5 is an excellent PU.1/IRF-4 half site (Brass et al., 1996; Eisenbeis et al., 1995; Marecki and Fenton, 2000).”
BackgroundRegulation of T helper cell differentiation by interferon regulatory factor family members
Zhang, R., Chen, K., Peng, L., & Xiong, H. (2012) · Immunologic Research · doi:10.1007/s12026-012-8328-0 · Cited by 33
“1 to relieve the inhibition from the auto-inhibitory domain, it becomes a strong transcriptional activator of its target genes [89].”
BackgroundStructural Studies of IRF4 Reveal a Flexible Autoinhibitory Region and a Compact Linker Domain
Remesh, S. G., Santosh, V., & Escalante, C. R. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.678789 · Cited by 33
“Indeed, a study by Mamane et al. (59) showed that FKBP52, a peptidyl-prolyl isomerase, inhibited the transactivation activity of IRF4 and binding to EICE DNA sites.”
BackgroundInfluentialSpi-C Has Opposing Effects to PU.1 on Gene Expression in Progenitor B Cells
Schweitzer, B. L., Huang, K. J., Kamath, M. B., Emelyanov, A. V., Birshtein, B. K., & DeKoter, R. P. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.4.2195 · Cited by 31
“Spi-C cDNA was cloned into the hemagglutinin (HA) tag-containing pcDNA3 vector described previously (36) using the NotI and ApaI restriction sites.”
BackgroundMethodGenomic programming of IRF4-expressing human Langerhans cells
Sirvent, S., Vallejo, A. F., Davies, J., Clayton, K., Wu, Z., Woo, J., Riddell, J., Chaudhri, V. K., Stumpf, P. S., Nazlamova, L., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14125-x · Cited by 31
Self-citationStructural determinants of the IRF4/DNA homodimeric complex
Sundararaj, S., Seneviratne, S., Williams, S. J., Enders, A., & Casarotto, M. G. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1287 · Cited by 34
“Notably, IAD also contains a C-terminal auto-* inhibitory region (AR) which directly binds the DBD and modulates its interaction with the target DNA (19,21,22).”
A Role for Interferon Regulatory Factor 4 in Receptor Editing
Pathak, S., Ma, S., Trinh, L., & Lu, R. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01946-07 · Cited by 33
“In contrast, the activation of the Ig locus by IRF-4 is most likely mediated by interaction with the Ets family transcription factors PU.1 and Spi-B (3, 4); it has been shown that , but not , transcription is severely impaired in the PU.1 and Spi-B double-deficient pre-B cells, indicating that the interaction between…”
BackgroundInfluentialImplication of IRF4 Aberrant Gene Expression in the Acute Leukemias of Childhood
Adamaki, M., Lambrou, G. Ι., Athanasiadou, A., Tzanoudaki, M., Vlahopoulos, S., & Moschovi, M. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072326 · Cited by 28
“It has already been demonstrated that IRF4 is expressed at varying levels throughout B-cell development, with expression peaking in plasma cells, therefore varying transcript levels in human malignancies could mirror IRF4 expression in normal lymphoid activation and differentiation [35,36].”
BackgroundMotif grammar: The basis of the language of gene expression
Nagy, G., & Nagy, L. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.07.007 · Cited by 31
Review: IRF-4 Activities in HTLV-I-Induced T Cell Leukemogenesis
Mamane, Y., Sharma, S., Grandvaux, N., Hernandez, E., & Hiscott, J. B. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452746 · Cited by 28
“(8,9,63) 66) IRF-4 can also cooperate with other transcription factors, such as E47 and Stat6, to modulate gene expression.”
Cook, S. L., Franke, M. C., Sievert, E. P., & Sciammas, R. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.05.001 · Cited by 26
The Igκ3′ Enhancer Is Activated by Gradients of Chromatin Accessibility and Protein Association
McDevit, D. C., Perkins, L., Atchison, M. L., & Nikolajczyk, B. S. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.5.2834 · Cited by 26
“6), although in agreement with relatively invariable IRF-4 mRNA levels before terminal B cell differentiation (45), do not completely agree with IRF-4 protein analysis in a separate developmental series of B cells, wherein IRF-4 levels increase at the pre-B to immature stage of B cell development (46).”
BackgroundResultSoodgupta, D., White, L. S., Yang, W., Johnston, R., Andrews, J. M., Kohyama, M., MURPHY, K. M. M., Mosammaparast, N., Payton, J. E., & Bednarski, J. J. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.026 · Cited by 25
“1 forms heterodimeric complexes with IRF4 or IRF8 to promote transcription (Brass et al., 1996; Heinz et al., 2010; Pongubala et al., 1992).”
BackgroundDilworth, D., Gudavicius, G., Leung, A., & Nelson, C. J. (2012) · Biochemistry and Cell Biology · doi:10.1139/o11-045 · Cited by 25
Ma, S., Shukla, V., Fang, L., Gould, K. A., Joshi, S. S., & Lu, R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.475913 · Cited by 24
“Because theDNAbinding domain of IRF4 contains a nuclear localization signal, the truncated IRF4 is localized predominantly in the cytosol (49, 50).”
BackgroundMutants of ETS domain PU.1 and GGAA/T recognition: Free energies and kinetics
Pio, F., Assa‐Munt, N., Yguerabide, J., & Maki, R. A. (1999) · Protein Science · doi:10.1110/ps.8.10.2098 · Cited by 22
“…composed of PU.1 or ETS-1 with other transcription factors binding to adjacent sites have been characterized ~Pongubala et al., 1992, 1993; Brass et al., 1996; Erman & Sen, 1996; Nikolajczyk et al., 1996!. Recently, the first crystal structure of the ETS domain of PU.1 complexed to DNA at…”
BackgroundCritical Functions of IRF4 in B and T Lymphocytes
Hagman, J. R. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1701385 · Cited by 22
“1 independent) regulator of transcription (6).”
Epigenetics and the IRFs: A complex interplay in the control of immunity and autoimmunity
Rogatsky, I., Chandrasekaran, U., Manni, M., Yi, W., & Pernis, A. B. (2013) · Autoimmunity · doi:10.3109/08916934.2013.853050 · Cited by 20
“While IRF4 was initially believed to be a lymphoid-specific member of the IRF family [128,129], it is also expressed in myeloid cells, particularly M2-type macrophages and myeloid dendritic cells, where, interestingly, its expression can be modulated by estrogen [126,130,131].”
BackgroundHematopoietic Stem Cell Molecular Targets and Factors Essential for Hematopoiesis
Raghav, P. K., & Gangenahalli, G. U. (2018) · Journal of Stem Cell Research & Therapy · doi:10.4172/2157-7633.1000441 · Cited by 22
“1 protein is the target of phosphorylation events, noticeable on serine 148 [49].”
BackgroundNagulapalli, S., Goheer, A., Pitt, L. K., McIntosh, L. P., & Atchison, M. L. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.20.7337-7350.2002 · Cited by 20
“Fulllength Pip does not bind to DNA efficiently, but a truncated Pip protein binds to DNA well (6, 7, 12, 45).”
BackgroundMolecular interactions of IRF4 in B cell development and malignancies
Sundararaj, S., & Casarotto, M. G. (2021) · Biophysical Reviews · doi:10.1007/s12551-021-00825-6 · Cited by 19
Exploring Functional Redundancy in the Immunoglobulin μ Heavy-Chain Gene Enhancer
Dang, W., Nikolajczyk, B. S., & Sen, R. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.11.6870 · Cited by 19
“The sequence for the lB probe used in the binding of HAPip1-380 is 59-GAGAAATAAAAGGAAGTGAAACCAAG-39.”
MethodInfluentialBackbone dynamics of a short PU.1 ETS domain 1 1Edited by P. E. Wright
Jia, X., Lee, L. K., Light, J. P., Palmer, A. G. I., & Assa‐Munt, N. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3123 · Cited by 18
Thouenon, R., Chentout, L., Moreno-Corona, N. C., Poggi, L., Lombardi, E. P., Hoareau‐Coudert, B., Schmitt, Y., Lagresle‐Peyrou, C., Bustamante, J. C., André‐Schmutz, I., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20221292 · Cited by 17
“1, SPIB, or BATF transcription factors, IRF4 binds to erythroblast-transformation-specific interferon composite elements (EICEs) or AP-1-IRF composite elements (AICE 1 or 2), respectively, and thus mediates transcriptional activity (Brass et al., 1996; Li et al., 2012; Ochiai et al., 2013).”
BackgroundXAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7
Liu, B., Liu, R., Li, W., Mao, X.-T., Li, Y., Huang, T., Wang, H., Chen, H., Zhong, J.-Y., Yang, B., et al. (2022) · EMBO Reports · doi:10.15252/embr.202255387 · Cited by 17
“IRF4 and IRF8, identified later, were found to exhibit physiological functions similar to those of IRF2; however, the functions of IRF4 and IRF8 are multifaceted, as they exhibit opposite functions in different complexes (Nelson et al , 1993; Brass et al , 1996; Shaffer et al , 2009).”
Interferon Regulatory Factor 8 (IRF8) Interacts with the B Cell Lymphoma 6 (BCL6) Corepressor BCOR
Yoon, J., Feng, X., Kim, Y., Shin, D., Hatzi, K., Wang, H., & Morse, H. C. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.571182 · Cited by 19
Crystallization and characterization of PU.1/IRF-4/DNA ternary complex
Escalante, C. R., Shen, L., Escalante, M. C., Brass, A. L., Edwards, T. A., Singh, H., & Aggarwal, A. K. (2002) · Journal of Structural Biology · doi:10.1016/s1047-8477(02)00514-2 · Cited by 17
Self-citationGuo, Z., Xu, P., Ge, S., Zhang, C., Zheng, X., Xu, J., Liu, Z., Li, B., & Ge, S. (2017) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2017.3087 · Cited by 16
“The IRF4 protein (full-length 1-450) possesses an NH2-terminal (1-134) DNA binding domain, a activation domain region that includes a proline-rich segment, and the COOH-terminal contains the regulatory domain (19,20).”
Functional interaction of CARD15/NOD2 and Crohn’s disease-associated TNFα polymorphisms
Linderson, Y., Bresso, F., Buentke, E., Pettersson, S., & D’Amato, M. (2005) · International Journal of Colorectal Disease · doi:10.1007/s00384-004-0732-z · Cited by 15
“The TNFα probe used for shift assays has been previously described [15], as well as the NF-κB and PU.1 probes used for specific and non-specific competition respectively [21, 22 ].”
MethodHeydemann, A., Boehmler, J. H., & Simon, M. C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.47.29527 · Cited by 15
The hematopoietic cell-specific transcription factor PU.1 is critical for expression of CD11c
Yashiro, T., Kasakura, K., Oda, Y., Kitamura, N., Inoue, A., Nakamura, S., Yokoyama, H., Fukuyama, K., Hara, M., Ogawa, H., et al. (2017) · International Immunology · doi:10.1093/intimm/dxx009 · Cited by 14
DNA binding and transcription activation by chicken interferon regulatory factor-3 (chIRF-3)
Grant, C. E. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.23.4790 · Cited by 12
IRF-4 Suppresses BCR/ABL Transformation of Myeloid Cells in a DNA Binding-independent Manner
Jo, S., & Ren, R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.289728 · Cited by 11
“1 binding mutants of IRF-4, AS397 and 1–380 (27, 35).”
IRF4 promotes Epstein–Barr virus activation in Burkitt’s lymphoma cells
Gao, Y., Wang, L., Lei, Z., Li, J., Forrest, J. C., & Liang, X. (2019) · Journal of General Virology · doi:10.1099/jgv.0.001249 · Cited by 11
Interferon Induces Up-regulation of Spi-1/PU.1 in Human Leukemia K562 Cells
Gutiérrez, P., Delgado, M. D., Richard, C., Moreau-Gachelin, F., & León, J. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7760 · Cited by 12
Hodawadekar, S., Park, K., Farrar, M. A., & Atchison, M. L. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102239 · Cited by 10
Yasui, K., Izumida, M., Nakagawa, T., Kubo, Y., Hayashi, H., Ito, T., Ikeda, H., & Matsuyama, T. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.04.159 · Cited by 10
Johnson, K. D., Jung, M. M., Tran, V. L., & Bresnick, E. H. (2023) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000763 · Cited by 9
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
