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. 1998 Jun 1;17(11):3124–3134. doi: 10.1093/emboj/17.11.3124

Modulation of cytokine-induced HIV gene expression by competitive binding of transcription factors to the coactivator p300.

M O Hottiger 1, L K Felzien 1, G J Nabel 1
PMCID: PMC1170651  PMID: 9606194

Abstract

The host response to viral infection involves the secretion of multiple cytokines which alter immune function and viral replication. These proteins activate several signal transduction pathways in infected cells which must be integrated to regulate cellular and viral gene expression. In this report, we demonstrate that specific transcription factors induced by distinct cytokines regulate HIV transcription by competitive binding to the p300 coactivator. Interferon-alpha (IFN-alpha) was found to inhibit NF-kappaB-dependent HIV gene expression stimulated by tumor necrosis factor-alpha (TNF-alpha). This inhibition was mediated by binding of the IFN-alpha signal transducer and activator of transcription 2, Stat2, to a specific domain of p300 which also binds to the RelA (p65) subunit of NF-kappaB. p300 was found to be limiting with respect to RelA (p65) and Stat2, and this effect was reversed by overexpression of p300. Inhibition by Stat2 was specific for NF-kappaB and was not mediated by Stat1, which is also induced by IFN-alpha. Gene activation induced by the Stat2 transcription domain was also inhibited by expression of RelA. These results demonstrate that HIV transcription can be regulated in the nucleus by competitive binding of specific cytokine-induced transcription factors to a discrete domain of a transcriptional coactivator.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguilar-Cordova E., Chinen J., Donehower L., Lewis D. E., Belmont J. W. A sensitive reporter cell line for HIV-1 tat activity, HIV-1 inhibitors, and T cell activation effects. AIDS Res Hum Retroviruses. 1994 Mar;10(3):295–301. doi: 10.1089/aid.1994.10.295. [DOI] [PubMed] [Google Scholar]
  2. Agy M. B., Acker R. L., Sherbert C. H., Katze M. G. Interferon treatment inhibits virus replication in HIV-1- and SIV-infected CD4+ T-cell lines by distinct mechanisms: evidence for decreased stability and aberrant processing of HIV-1 proteins. Virology. 1995 Dec 20;214(2):379–386. doi: 10.1006/viro.1995.0047. [DOI] [PubMed] [Google Scholar]
  3. Baca-Regen L., Heinzinger N., Stevenson M., Gendelman H. E. Alpha interferon-induced antiretroviral activities: restriction of viral nucleic acid synthesis and progeny virion production in human immunodeficiency virus type 1-infected monocytes. J Virol. 1994 Nov;68(11):7559–7565. doi: 10.1128/jvi.68.11.7559-7565.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baeuerle P. A., Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179. doi: 10.1146/annurev.iy.12.040194.001041. [DOI] [PubMed] [Google Scholar]
  5. Bannister A. J., Kouzarides T. CBP-induced stimulation of c-Fos activity is abrogated by E1A. EMBO J. 1995 Oct 2;14(19):4758–4762. doi: 10.1002/j.1460-2075.1995.tb00157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bannister A. J., Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature. 1996 Dec 19;384(6610):641–643. doi: 10.1038/384641a0. [DOI] [PubMed] [Google Scholar]
  7. Bannister A. J., Oehler T., Wilhelm D., Angel P., Kouzarides T. Stimulation of c-Jun activity by CBP: c-Jun residues Ser63/73 are required for CBP induced stimulation in vivo and CBP binding in vitro. Oncogene. 1995 Dec 21;11(12):2509–2514. [PubMed] [Google Scholar]
  8. Beg A. A., Baldwin A. S., Jr The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors. Genes Dev. 1993 Nov;7(11):2064–2070. doi: 10.1101/gad.7.11.2064. [DOI] [PubMed] [Google Scholar]
  9. Beg A. A., Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science. 1996 Nov 1;274(5288):782–784. doi: 10.1126/science.274.5288.782. [DOI] [PubMed] [Google Scholar]
  10. Bhattacharya S., Eckner R., Grossman S., Oldread E., Arany Z., D'Andrea A., Livingston D. M. Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha. Nature. 1996 Sep 26;383(6598):344–347. doi: 10.1038/383344a0. [DOI] [PubMed] [Google Scholar]
  11. Bourinbaiar A. S., Krasinski K., Borkowsky W., Lee-Huang S. Protective effect of interferon-alpha against cell-mediated human immunodeficiency virus transmission resulting from coculture of infected lymphocytes with fetal trophoblasts. J Interferon Cytokine Res. 1995 Jun;15(6):503–508. doi: 10.1089/jir.1995.15.503. [DOI] [PubMed] [Google Scholar]
  12. Brinchmann J. E., Gaudernack G., Vartdal F. In vitro replication of HIV-1 in naturally infected CD4+ T cells is inhibited by rIFN alpha 2 and by a soluble factor secreted by activated CD8+ T cells, but not by rIFN beta, rIFN gamma, or recombinant tumor necrosis factor-alpha. J Acquir Immune Defic Syndr. 1991;4(5):480–488. [PubMed] [Google Scholar]
  13. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chrivia J. C., Kwok R. P., Lamb N., Hagiwara M., Montminy M. R., Goodman R. H. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 1993 Oct 28;365(6449):855–859. doi: 10.1038/365855a0. [DOI] [PubMed] [Google Scholar]
  15. Coccia E. M., Krust B., Hovanessian A. G. Specific inhibition of viral protein synthesis in HIV-infected cells in response to interferon treatment. J Biol Chem. 1994 Sep 16;269(37):23087–23094. [PubMed] [Google Scholar]
  16. Dai P., Akimaru H., Tanaka Y., Hou D. X., Yasukawa T., Kanei-Ishii C., Takahashi T., Ishii S. CBP as a transcriptional coactivator of c-Myb. Genes Dev. 1996 Mar 1;10(5):528–540. doi: 10.1101/gad.10.5.528. [DOI] [PubMed] [Google Scholar]
  17. Darnell J. E., Jr, Kerr I. M., Stark G. R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. doi: 10.1126/science.8197455. [DOI] [PubMed] [Google Scholar]
  18. Dorr R. T. Interferon-alpha in malignant and viral diseases. A review. Drugs. 1993 Feb;45(2):177–211. doi: 10.2165/00003495-199345020-00003. [DOI] [PubMed] [Google Scholar]
  19. Eckner R., Ewen M. E., Newsome D., Gerdes M., DeCaprio J. A., Lawrence J. B., Livingston D. M. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev. 1994 Apr 15;8(8):869–884. doi: 10.1101/gad.8.8.869. [DOI] [PubMed] [Google Scholar]
  20. Eckner R., Yao T. P., Oldread E., Livingston D. M. Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation. Genes Dev. 1996 Oct 1;10(19):2478–2490. doi: 10.1101/gad.10.19.2478. [DOI] [PubMed] [Google Scholar]
  21. Eckner R. p300 and CBP as transcriptional regulators and targets of oncogenic events. Biol Chem. 1996 Nov;377(11):685–688. [PubMed] [Google Scholar]
  22. Fan S. X., Skillman D. R., Liao M. J., Testa D., Meltzer M. S. Increased efficacy of human natural interferon alpha (IFN-alpha n3) versus human recombinant IFN-alpha 2 for inhibition of HIV-1 replication in primary human monocytes. AIDS Res Hum Retroviruses. 1993 Nov;9(11):1115–1122. doi: 10.1089/aid.1993.9.1115. [DOI] [PubMed] [Google Scholar]
  23. Gendelman H. E., Baca L. M., Turpin J., Kalter D. C., Hansen B., Orenstein J. M., Dieffenbach C. W., Friedman R. M., Meltzer M. S. Regulation of HIV replication in infected monocytes by IFN-alpha. Mechanisms for viral restriction. J Immunol. 1990 Oct 15;145(8):2669–2676. [PubMed] [Google Scholar]
  24. Gendelman H. E., Baca L., Turpin J. A., Kalter D. C., Hansen B. D., Orenstein J. M., Friedman R. M., Meltzer M. S. Restriction of HIV replication in infected T cells and monocytes by interferon-alpha. AIDS Res Hum Retroviruses. 1990 Aug;6(8):1045–1049. doi: 10.1089/aid.1990.6.1045. [DOI] [PubMed] [Google Scholar]
  25. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gu W., Shi X. L., Roeder R. G. Synergistic activation of transcription by CBP and p53. Nature. 1997 Jun 19;387(6635):819–823. doi: 10.1038/42972. [DOI] [PubMed] [Google Scholar]
  27. Hartshorn K. L., Neumeyer D., Vogt M. W., Schooley R. T., Hirsch M. S. Activity of interferons alpha, beta, and gamma against human immunodeficiency virus replication in vitro. AIDS Res Hum Retroviruses. 1987 Summer;3(2):125–133. doi: 10.1089/aid.1987.3.125. [DOI] [PubMed] [Google Scholar]
  28. Havell E. A., Fiers W., North R. J. The antitumor function of tumor necrosis factor (TNF), I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity. J Exp Med. 1988 Mar 1;167(3):1067–1085. doi: 10.1084/jem.167.3.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hill C. S., Treisman R. Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell. 1995 Jan 27;80(2):199–211. doi: 10.1016/0092-8674(95)90403-4. [DOI] [PubMed] [Google Scholar]
  30. Horvai A. E., Xu L., Korzus E., Brard G., Kalafus D., Mullen T. M., Rose D. W., Rosenfeld M. G., Glass C. K. Nuclear integration of JAK/STAT and Ras/AP-1 signaling by CBP and p300. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1074–1079. doi: 10.1073/pnas.94.4.1074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Howe J. A., Bayley S. T. Effects of Ad5 E1A mutant viruses on the cell cycle in relation to the binding of cellular proteins including the retinoblastoma protein and cyclin A. Virology. 1992 Jan;186(1):15–24. doi: 10.1016/0042-6822(92)90057-v. [DOI] [PubMed] [Google Scholar]
  32. Janknecht R., Hunter T. Versatile molecular glue. Transcriptional control. Curr Biol. 1996 Aug 1;6(8):951–954. doi: 10.1016/s0960-9822(02)00636-x. [DOI] [PubMed] [Google Scholar]
  33. Janknecht R., Nordheim A. Regulation of the c-fos promoter by the ternary complex factor Sap-1a and its coactivator CBP. Oncogene. 1996 May 2;12(9):1961–1969. [PubMed] [Google Scholar]
  34. Kamei Y., Xu L., Heinzel T., Torchia J., Kurokawa R., Gloss B., Lin S. C., Heyman R. A., Rose D. W., Glass C. K. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell. 1996 May 3;85(3):403–414. doi: 10.1016/s0092-8674(00)81118-6. [DOI] [PubMed] [Google Scholar]
  35. Kornbluth R. S., Oh P. S., Munis J. R., Cleveland P. H., Richman D. D. The role of interferons in the control of HIV replication in macrophages. Clin Immunol Immunopathol. 1990 Feb;54(2):200–219. doi: 10.1016/0090-1229(90)90082-2. [DOI] [PubMed] [Google Scholar]
  36. Kwok R. P., Lundblad J. R., Chrivia J. C., Richards J. P., Bächinger H. P., Brennan R. G., Roberts S. G., Green M. R., Goodman R. H. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature. 1994 Jul 21;370(6486):223–226. doi: 10.1038/370223a0. [DOI] [PubMed] [Google Scholar]
  37. Lee J. S., Galvin K. M., See R. H., Eckner R., Livingston D., Moran E., Shi Y. Relief of YY1 transcriptional repression by adenovirus E1A is mediated by E1A-associated protein p300. Genes Dev. 1995 May 15;9(10):1188–1198. doi: 10.1101/gad.9.10.1188. [DOI] [PubMed] [Google Scholar]
  38. Leung K., Nabel G. J. HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor. Nature. 1988 Jun 23;333(6175):776–778. doi: 10.1038/333776a0. [DOI] [PubMed] [Google Scholar]
  39. Lill N. L., Grossman S. R., Ginsberg D., DeCaprio J., Livingston D. M. Binding and modulation of p53 by p300/CBP coactivators. Nature. 1997 Jun 19;387(6635):823–827. doi: 10.1038/42981. [DOI] [PubMed] [Google Scholar]
  40. Lill N. L., Tevethia M. J., Eckner R., Livingston D. M., Modjtahedi N. p300 family members associate with the carboxyl terminus of simian virus 40 large tumor antigen. J Virol. 1997 Jan;71(1):129–137. doi: 10.1128/jvi.71.1.129-137.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lillie J. W., Green M. R. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. doi: 10.1038/338039a0. [DOI] [PubMed] [Google Scholar]
  42. Marshall C. J. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 1995 Jan 27;80(2):179–185. doi: 10.1016/0092-8674(95)90401-8. [DOI] [PubMed] [Google Scholar]
  43. Meylan P. R., Guatelli J. C., Munis J. R., Richman D. D., Kornbluth R. S. Mechanisms for the inhibition of HIV replication by interferons-alpha, -beta, and -gamma in primary human macrophages. Virology. 1993 Mar;193(1):138–148. doi: 10.1006/viro.1993.1110. [DOI] [PubMed] [Google Scholar]
  44. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  45. Nakajima T., Fukamizu A., Takahashi J., Gage F. H., Fisher T., Blenis J., Montminy M. R. The signal-dependent coactivator CBP is a nuclear target for pp90RSK. Cell. 1996 Aug 9;86(3):465–474. doi: 10.1016/s0092-8674(00)80119-1. [DOI] [PubMed] [Google Scholar]
  46. Natesan S., Rivera V. M., Molinari E., Gilman M. Transcriptional squelching re-examined. Nature. 1997 Nov 27;390(6658):349–350. doi: 10.1038/37019. [DOI] [PubMed] [Google Scholar]
  47. Oelgeschläger M., Janknecht R., Krieg J., Schreek S., Lüscher B. Interaction of the co-activator CBP with Myb proteins: effects on Myb-specific transactivation and on the cooperativity with NF-M. EMBO J. 1996 Jun 3;15(11):2771–2780. [PMC free article] [PubMed] [Google Scholar]
  48. Ogryzko V. V., Schiltz R. L., Russanova V., Howard B. H., Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996 Nov 29;87(5):953–959. doi: 10.1016/s0092-8674(00)82001-2. [DOI] [PubMed] [Google Scholar]
  49. Perkins N. D., Agranoff A. B., Duckett C. S., Nabel G. J. Transcription factor AP-2 regulates human immunodeficiency virus type 1 gene expression. J Virol. 1994 Oct;68(10):6820–6823. doi: 10.1128/jvi.68.10.6820-6823.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Perkins N. D., Agranoff A. B., Pascal E., Nabel G. J. An interaction between the DNA-binding domains of RelA(p65) and Sp1 mediates human immunodeficiency virus gene activation. Mol Cell Biol. 1994 Oct;14(10):6570–6583. doi: 10.1128/mcb.14.10.6570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Perkins N. D., Felzien L. K., Betts J. C., Leung K., Beach D. H., Nabel G. J. Regulation of NF-kappaB by cyclin-dependent kinases associated with the p300 coactivator. Science. 1997 Jan 24;275(5299):523–527. doi: 10.1126/science.275.5299.523. [DOI] [PubMed] [Google Scholar]
  52. Petrij F., Giles R. H., Dauwerse H. G., Saris J. J., Hennekam R. C., Masuno M., Tommerup N., van Ommen G. J., Goodman R. H., Peters D. J. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature. 1995 Jul 27;376(6538):348–351. doi: 10.1038/376348a0. [DOI] [PubMed] [Google Scholar]
  53. Pitha P. M. Multiple effects of interferon on HIV-1 replication. J Interferon Res. 1991 Dec;11(6):313–318. doi: 10.1089/jir.1991.11.313. [DOI] [PubMed] [Google Scholar]
  54. Poli G., Orenstein J. M., Kinter A., Folks T. M., Fauci A. S. Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines. Science. 1989 May 5;244(4904):575–577. doi: 10.1126/science.2470148. [DOI] [PubMed] [Google Scholar]
  55. Popik W., Pitha P. M. Transcriptional activation of the tat-defective human immunodeficiency virus type-1 provirus: effect of interferon. Virology. 1992 Aug;189(2):435–447. doi: 10.1016/0042-6822(92)90567-9. [DOI] [PubMed] [Google Scholar]
  56. Qureshi S. A., Leung S., Kerr I. M., Stark G. R., Darnell J. E., Jr Function of Stat2 protein in transcriptional activation by alpha interferon. Mol Cell Biol. 1996 Jan;16(1):288–293. doi: 10.1128/mcb.16.1.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Sadowski I., Ptashne M. A vector for expressing GAL4(1-147) fusions in mammalian cells. Nucleic Acids Res. 1989 Sep 25;17(18):7539–7539. doi: 10.1093/nar/17.18.7539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Schindler C., Darnell J. E., Jr Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu Rev Biochem. 1995;64:621–651. doi: 10.1146/annurev.bi.64.070195.003201. [DOI] [PubMed] [Google Scholar]
  59. Schindler C., Fu X. Y., Improta T., Aebersold R., Darnell J. E., Jr Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7836–7839. doi: 10.1073/pnas.89.16.7836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Shiama N. The p300/CBP family: integrating signals with transcription factors and chromatin. Trends Cell Biol. 1997 Jun;7(6):230–236. doi: 10.1016/S0962-8924(97)01048-9. [DOI] [PubMed] [Google Scholar]
  61. Shirazi Y., Pitha P. M. Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle. J Virol. 1992 Mar;66(3):1321–1328. doi: 10.1128/jvi.66.3.1321-1328.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Shu H. B., Agranoff A. B., Nabel E. G., Leung K., Duckett C. S., Neish A. S., Collins T., Nabel G. J. Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells. Mol Cell Biol. 1993 Oct;13(10):6283–6289. doi: 10.1128/mcb.13.10.6283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Shuai K. Interferon-activated signal transduction to the nucleus. Curr Opin Cell Biol. 1994 Apr;6(2):253–259. doi: 10.1016/0955-0674(94)90144-9. [DOI] [PubMed] [Google Scholar]
  64. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  65. Smith M. S., Thresher R. J., Pagano J. S. Inhibition of human immunodeficiency virus type 1 morphogenesis in T cells by alpha interferon. Antimicrob Agents Chemother. 1991 Jan;35(1):62–67. doi: 10.1128/aac.35.1.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Torchia J., Rose D. W., Inostroza J., Kamei Y., Westin S., Glass C. K., Rosenfeld M. G. The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature. 1997 Jun 12;387(6634):677–684. doi: 10.1038/42652. [DOI] [PubMed] [Google Scholar]
  67. Van Antwerp D. J., Martin S. J., Kafri T., Green D. R., Verma I. M. Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science. 1996 Nov 1;274(5288):787–789. doi: 10.1126/science.274.5288.787. [DOI] [PubMed] [Google Scholar]
  68. Wang C. Y., Mayo M. W., Baldwin A. S., Jr TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science. 1996 Nov 1;274(5288):784–787. doi: 10.1126/science.274.5288.784. [DOI] [PubMed] [Google Scholar]
  69. Yamada O., Hattori N., Kurimura T., Kita M., Kishida T. Inhibition of growth of HIV by human natural interferon in vitro. AIDS Res Hum Retroviruses. 1988 Aug;4(4):287–294. doi: 10.1089/aid.1988.4.287. [DOI] [PubMed] [Google Scholar]
  70. Yang X. J., Ogryzko V. V., Nishikawa J., Howard B. H., Nakatani Y. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 1996 Jul 25;382(6589):319–324. doi: 10.1038/382319a0. [DOI] [PubMed] [Google Scholar]
  71. Yuan W., Condorelli G., Caruso M., Felsani A., Giordano A. Human p300 protein is a coactivator for the transcription factor MyoD. J Biol Chem. 1996 Apr 12;271(15):9009–9013. doi: 10.1074/jbc.271.15.9009. [DOI] [PubMed] [Google Scholar]
  72. Zhang J. J., Vinkemeier U., Gu W., Chakravarti D., Horvath C. M., Darnell J. E., Jr Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling. Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15092–15096. doi: 10.1073/pnas.93.26.15092. [DOI] [PMC free article] [PubMed] [Google Scholar]

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