Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex (original) (raw)
Abstract
The first STAT-containing transcription factor to be studied, the alpha-interferon-induced ISGF3, is composed of a Stat1:2 heterodimer and a weak DNA-binding protein, p48, that is a member of a growing family of proteins similar to the so-called interferon regulatory factor (IRF-1). The p48 and Stat1:2 heterodimer do not associate stably in the absence of DNA, but we show that amino acids approximately 150 to 250 of Stat1 and a COOH-terminal portion of p48 exhibit physical interaction, implying contact that stabilizes ISGF3. Moreover, amino acid exchanges within the Stat1 contact region diminish or abolish the functional activity of Stat1. This protein interaction domain may be important in other STAT proteins to recruit partners to multiprotein transcription factors.
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- Au W. C., Moore P. A., Lowther W., Juang Y. T., Pitha P. M. 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. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11657–11661. doi: 10.1073/pnas.92.25.11657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bluyssen H. A., Muzaffar R., Vlieststra R. J., van der Made A. C., Leung S., Stark G. R., Kerr I. M., Trapman J., Levy D. E. Combinatorial association and abundance of components of interferon-stimulated gene factor 3 dictate the selectivity of interferon responses. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5645–5649. doi: 10.1073/pnas.92.12.5645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bovolenta 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. Molecular interactions between interferon consensus sequence binding protein and members of the interferon regulatory factor family. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5046–5050. doi: 10.1073/pnas.91.11.5046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Driggers P. H., Ennist D. L., Gleason S. L., Mak W. H., Marks M. S., Levi B. Z., Flanagan J. R., Appella E., Ozato K. An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. Proc Natl Acad Sci U S A. 1990 May;87(10):3743–3747. doi: 10.1073/pnas.87.10.3743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fu X. Y., Kessler D. S., Veals S. A., Levy D. E., Darnell J. E., Jr ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8555–8559. doi: 10.1073/pnas.87.21.8555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fu X. Y., Schindler C., Improta T., Aebersold R., Darnell J. E., Jr The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7840–7843. doi: 10.1073/pnas.89.16.7840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenlund A. C., Farrar M. A., Viviano B. L., Schreiber R. D. Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91). EMBO J. 1994 Apr 1;13(7):1591–1600. doi: 10.1002/j.1460-2075.1994.tb06422.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gyuris J., Golemis E., Chertkov H., Brent R. Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell. 1993 Nov 19;75(4):791–803. doi: 10.1016/0092-8674(93)90498-f. [DOI] [PubMed] [Google Scholar]
- Harada H., Fujita T., Miyamoto M., Kimura Y., Maruyama M., Furia A., Miyata T., Taniguchi T. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 1989 Aug 25;58(4):729–739. doi: 10.1016/0092-8674(89)90107-4. [DOI] [PubMed] [Google Scholar]
- Heim M. H., Kerr I. M., Stark G. R., Darnell J. E., Jr Contribution of STAT SH2 groups to specific interferon signaling by the Jak-STAT pathway. Science. 1995 Mar 3;267(5202):1347–1349. doi: 10.1126/science.7871432. [DOI] [PubMed] [Google Scholar]
- Hill C. S., Treisman R. Differential activation of c-fos promoter elements by serum, lysophosphatidic acid, G proteins and polypeptide growth factors. EMBO J. 1995 Oct 16;14(20):5037–5047. doi: 10.1002/j.1460-2075.1995.tb00186.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horvath C. M., Wen Z., Darnell J. E., Jr A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain. Genes Dev. 1995 Apr 15;9(8):984–994. doi: 10.1101/gad.9.8.984. [DOI] [PubMed] [Google Scholar]
- Improta T., Schindler C., Horvath C. M., Kerr I. M., Stark G. R., Darnell J. E., Jr Transcription factor ISGF-3 formation requires phosphorylated Stat91 protein, but Stat113 protein is phosphorylated independently of Stat91 protein. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4776–4780. doi: 10.1073/pnas.91.11.4776. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kessler D. S., Levy D. E., Darnell J. E., Jr Two interferon-induced nuclear factors bind a single promoter element in interferon-stimulated genes. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8521–8525. doi: 10.1073/pnas.85.22.8521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kessler D. S., Veals S. A., Fu X. Y., Levy D. E. Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. Genes Dev. 1990 Oct;4(10):1753–1765. doi: 10.1101/gad.4.10.1753. [DOI] [PubMed] [Google Scholar]
- Leung S., Qureshi S. A., Kerr I. M., Darnell J. E., Jr, Stark G. R. Role of STAT2 in the alpha interferon signaling pathway. Mol Cell Biol. 1995 Mar;15(3):1312–1317. doi: 10.1128/mcb.15.3.1312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levy D. E., Lew D. J., Decker T., Kessler D. S., Darnell J. E., Jr Synergistic interaction between interferon-alpha and interferon-gamma through induced synthesis of one subunit of the transcription factor ISGF3. EMBO J. 1990 Apr;9(4):1105–1111. doi: 10.1002/j.1460-2075.1990.tb08216.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Look D. C., Pelletier M. R., Tidwell R. M., Roswit W. T., Holtzman M. J. Stat1 depends on transcriptional synergy with Sp1. J Biol Chem. 1995 Dec 22;270(51):30264–30267. doi: 10.1074/jbc.270.51.30264. [DOI] [PubMed] [Google Scholar]
- Matsuyama T., Grossman A., Mittrücker H. W., Siderovski D. P., Kiefer F., Kawakami T., Richardson C. D., Taniguchi T., Yoshinaga S. K., Mak T. W. Molecular cloning of LSIRF, a lymphoid-specific member of the interferon regulatory factor family that binds the interferon-stimulated response element (ISRE). Nucleic Acids Res. 1995 Jun 25;23(12):2127–2136. doi: 10.1093/nar/23.12.2127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKnight S. L. Transcription revisited: a commentary on the 1995 Cold Spring Harbor Laboratory meeting, "Mechanisms of Eukaryotic Transcription". Genes Dev. 1996 Feb 15;10(4):367–381. doi: 10.1101/gad.10.4.367. [DOI] [PubMed] [Google Scholar]
- Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi: 10.1016/s0092-8674(88)91307-4. [DOI] [PubMed] [Google Scholar]
- Müller M., Laxton C., Briscoe J., Schindler C., Improta T., Darnell J. E., Jr, Stark G. R., Kerr I. M. Complementation of a mutant cell line: central role of the 91 kDa polypeptide of ISGF3 in the interferon-alpha and -gamma signal transduction pathways. EMBO J. 1993 Nov;12(11):4221–4228. doi: 10.1002/j.1460-2075.1993.tb06106.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neish A. S., Read M. A., Thanos D., Pine R., Maniatis T., Collins T. Endothelial interferon regulatory factor 1 cooperates with NF-kappa B as a transcriptional activator of vascular cell adhesion molecule 1. Mol Cell Biol. 1995 May;15(5):2558–2569. doi: 10.1128/mcb.15.5.2558. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pellegrini S., John J., Shearer M., Kerr I. M., Stark G. R. Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway. Mol Cell Biol. 1989 Nov;9(11):4605–4612. doi: 10.1128/mcb.9.11.4605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Qureshi S. A., Salditt-Georgieff M., Darnell J. E., Jr Tyrosine-phosphorylated Stat1 and Stat2 plus a 48-kDa protein all contact DNA in forming interferon-stimulated-gene factor 3. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3829–3833. doi: 10.1073/pnas.92.9.3829. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reich N., Evans B., Levy D., Fahey D., Knight E., Jr, Darnell J. E., Jr Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6394–6398. doi: 10.1073/pnas.84.18.6394. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson L. M., Kerppola T. K., Vendrell M., Luk D., Smeyne R. J., Bocchiaro C., Morgan J. I., Curran T. Regulation of c-fos expression in transgenic mice requires multiple interdependent transcription control elements. Neuron. 1995 Feb;14(2):241–252. doi: 10.1016/0896-6273(95)90282-1. [DOI] [PubMed] [Google Scholar]
- Schaefer T. S., Sanders L. K., Nathans D. Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9097–9101. doi: 10.1073/pnas.92.20.9097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Schindler C., Shuai K., Prezioso V. R., Darnell J. E., Jr Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science. 1992 Aug 7;257(5071):809–813. doi: 10.1126/science.1496401. [DOI] [PubMed] [Google Scholar]
- Sharf R., Azriel A., Lejbkowicz F., Winograd S. S., Ehrlich R., Levi B. Z. Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors. J Biol Chem. 1995 Jun 2;270(22):13063–13069. doi: 10.1074/jbc.270.22.13063. [DOI] [PubMed] [Google Scholar]
- Shuai K., Horvath C. M., Huang L. H., Qureshi S. A., Cowburn D., Darnell J. E., Jr Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell. 1994 Mar 11;76(5):821–828. doi: 10.1016/0092-8674(94)90357-3. [DOI] [PubMed] [Google Scholar]
- Shuai K., Schindler C., Prezioso V. R., Darnell J. E., Jr Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science. 1992 Dec 11;258(5089):1808–1812. doi: 10.1126/science.1281555. [DOI] [PubMed] [Google Scholar]
- Songyang Z., Shoelson S. E., Chaudhuri M., Gish G., Pawson T., Haser W. G., King F., Roberts T., Ratnofsky S., Lechleider R. J. SH2 domains recognize specific phosphopeptide sequences. Cell. 1993 Mar 12;72(5):767–778. doi: 10.1016/0092-8674(93)90404-e. [DOI] [PubMed] [Google Scholar]
- Stahl N., Farruggella T. J., Boulton T. G., Zhong Z., Darnell J. E., Jr, Yancopoulos G. D. Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors. Science. 1995 Mar 3;267(5202):1349–1353. doi: 10.1126/science.7871433. [DOI] [PubMed] [Google Scholar]
- Thanos D., Maniatis T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell. 1995 Dec 29;83(7):1091–1100. doi: 10.1016/0092-8674(95)90136-1. [DOI] [PubMed] [Google Scholar]
- Veals S. A., Santa Maria T., Levy D. E. Two domains of ISGF3 gamma that mediate protein-DNA and protein-protein interactions during transcription factor assembly contribute to DNA-binding specificity. Mol Cell Biol. 1993 Jan;13(1):196–206. doi: 10.1128/mcb.13.1.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Veals S. A., Schindler C., Leonard D., Fu X. Y., Aebersold R., Darnell J. E., Jr, Levy D. E. Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. Mol Cell Biol. 1992 Aug;12(8):3315–3324. doi: 10.1128/mcb.12.8.3315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson P. A., Melton D. A. Mesodermal patterning by an inducer gradient depends on secondary cell-cell communication. Curr Biol. 1994 Aug 1;4(8):676–686. doi: 10.1016/s0960-9822(00)00152-4. [DOI] [PubMed] [Google Scholar]