Three-dimensional structure of the Stat3β homodimer bound to DNA

Becker, Stefan; Groner, Bernd; Müller, Christoph W.

doi:10.1038/28101

Cited by 770 publications

(811 citation statements)

References 43 publications

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“…7B). The search strategy also indicated that the helical pattern of UXT was homologous to the last three helices of the 4-helix bundle of transcription factor STAT (signal transducers and activators of transcription) 3b (P42227, residues 136-321) [32] (Fig. 7C).…”

Section: Uxt (Xp_033860)-mentioning

confidence: 95%

Sequence Analysis of LRPPRC and Its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal Organization, Vesicular Trafficking, Nucleocytosolic Shuttling, and Chromosome Activity

2002

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LRPPRC (originally called LRP130) is an intracellular 130-kDa leucine-rich protein that copurifies with the FGF receptor from liver cell extracts and has been detected in diverse multiprotein complexes from the cell membrane, cytoskeleton and nucleus. Here we report results of a sequence homology analysis of LRPPRC and its SEC1 domain interactive partners. Twenty-three copies of tandem repeats that are similar to PPR, TPR and HEAT repeats characterize the LRPPRC sequence. The N-terminus exhibits multiple copies of leucine-rich nuclear transport signals followed by ENTH, DUF28 and SEC1 homology domains. We used the SEC1 domain to trap interactive partners expressed from a human liver cDNA library. Interactive C19ORF5 (XP_038600) exhibited a strong homology to microtubule-associated proteins (MAP) and a potential arginine-rich mRNA binding motif. UXT (XP_033860) exhibited α-helical properties homologous to the actin-associated spectrin repeat and L/I heptad repeats in mobile transcription factors. C6ORF34 (XP_004305) was homologous to the non-DNA binding C-terminus of the E. coli Rob transcription factor. CECR2 (AAK15343) exhibited a transcription factor AT-hook motif next to two bromodomains and a homology to guanylate-binding protein 1. Taken together these features suggest a regulatory role of LRPPRC and its SEC1 domain-interactive partners in integration of cytoskeletal networks with vesicular trafficking, nucleocytosolic shuttling, chromosome remodeling and transcription.

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Section: Uxt (Xp_033860)-mentioning

confidence: 95%

Sequence Analysis of LRPPRC and Its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal Organization, Vesicular Trafficking, Nucleocytosolic Shuttling, and Chromosome Activity

2002

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“…These results strongly suggest that Stat3 activation is required for IL-6-induced di erentiation in the M1 macrophage model. Interest- Chen et al, 1998;Becker et al, 1998), the overall organization of Stats consists of an N-terminal domain (N) involved in cooperative binding to DNA, a four-helix bundle (4HB), a b-barrel (bBBL) which forms loops involved in DNA binding, the SH2 domain (SH2) and conserved tyrosine phosphorylation site (Y P ) which are essential for dimerization, and a C-terminal region involved in transactivation of transcription (AD). Three types of dominant-negative mutants are illustrated.…”

Section: Dominant-negative Mutants Implicate Stat3 In Myeloid Differementioning

confidence: 99%

Control of myeloid differentiation and survival by Stats

et al. 2000

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Hematopoiesis involves a complex array of growth factors that regulate the survival and proliferation of immature progenitors, in¯uence di erentiation commitment, and modulate end-stage cell functions. This minireview is focused on the role of Stat activation in the development of myeloid cells in response to hematopoietic cytokines. Much of the evidence implicating Stats in these cellular processes comes from studies of mutant cytokine receptors selectively uncoupled from Stat activation, dominant-inhibitory Stat mutants, and mice with targeted disruptions of Stat genes. Together these approaches provide strong evidence that Stat activation, particularly of Stat3 and Stat5, plays an important role in myeloid di erentiation and survival. Oncogene (2000) 19, 2612 ± 2618.Keywords: stat; cytokine; di erentiation; survival; tyrosine kinase Mutant cytokine receptors lacking Stat recruitment sites fail to induce di erentiation gp130-based receptor system IL-6 and the related cytokines LIF, CNTF, OSM, IL-11 and CT-1 share structural features and a ect an overlapping set of target cells . The receptors for the IL-6 family of cytokines share a signal transducing subunit known as gp130, which provides a link to multiple signaling pathways via a tyrosine phosphorylation-dependent mechanism. This familiar signaling paradigm, shared by all of the cytokine receptor systems discussed here, is initiated by liganddependent receptor oligomerization, activation of receptor-associated tyrosine kinases, and phosphorylation of speci®c tyrosine residues within the receptor. A subset of these receptor phosphotyrosines recruit cytoplasmic Stats through their SH2 domains. The Stats are then phosphorylated by receptor-associated kinases, inducing dimerization, nuclear translocation, and transcriptional activation at speci®c promoter elements. As described in more detail below, regions of gp130 required for myeloid di erentiation are often required for Stat activation.The cytoplasmic region of gp130 responsible for Stat3 activation is also required for di erentiation signaling in the murine leukemia cell line, M1 . Both IL-6 and LIF induce growth arrest and macrophage di erentiation in this cell line. To avoid the complication of signaling from endogenous gp130, chimeric receptors were constructed in which the cytoplasmic region of gp130 was fused to the extracellular ligand-binding domain of growth hormone. The resulting chimeric receptor generated growth hormone-dependent signals for growth arrest and morphological changes indistinguishable from those of IL-6. Successive C-terminal truncations of the chimeric receptor identi®ed the distal 133 residues of gp130 as critical for the generation of signals for growth arrest, macrophage di erentiation, and Stat3 activation. Phosphorylation of Tyr 126 in this region of gp130 forms a binding site for the Stat3 SH2 domain (Y P XXQ motif) (Stahl et al., 1995). Mutagenesis of this site completely blocked di erentiation signaling and Stat3 activation from the truncated receptor. However, mutagenes...

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“…Stat3 contains several functional domains including the Nterminal domain (ND), coiled-coil domain with four ␣-helices (CC), DNA binding domain (DB), linker domain (LK), SH2 domain, and C-terminal domain (CT) (Becker et al, 1998). To define the domain that binds to Isl1, we generated a series of FLAG-tagged truncation mutants of Stat3 that encode individual domains or their combinations as illustrated in Figure 5A.…”

Section: Mapping the Binding Domains Mediating Interaction Between Ismentioning

confidence: 99%

The LIM/Homeodomain Protein Islet1 Recruits Janus Tyrosine Kinases and Signal Transducer and Activator of Transcription 3 and Stimulates Their Activities

Hao

Novotny‐Diermayr

Bian

et al. 2005

MBoC

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Islet1 (Isl1) belongs to the LIM homeodomain transcription factor family. Its roles in differentiation of motor neurons and organogenesis of pancreas and heart have been revealed. However, less is known about its regulatory mechanism and the target genes. In this study, we identified interactions between Isl1 and Janus tyrosine kinase (JAK), as well as signal transducer and activator of transcription (Stat)3, but not Stat1 and Stat5, in mammalian cells. We found that Isl1 not only forms a complex with Jak1 and Stat3 but also triggers the tyrosine phosphorylation of Jak1 and its kinase activity, thereby elevating the tyrosine phosphorylation, DNA binding activity, and target gene expression of Stat3. In vivo, the tyrosine-

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Three-dimensional structure of the Stat3β homodimer bound to DNA

Cited by 770 publications

References 43 publications

Sequence Analysis of LRPPRC and Its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal Organization, Vesicular Trafficking, Nucleocytosolic Shuttling, and Chromosome Activity

Sequence Analysis of LRPPRC and Its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal Organization, Vesicular Trafficking, Nucleocytosolic Shuttling, and Chromosome Activity

Control of myeloid differentiation and survival by Stats

The LIM/Homeodomain Protein Islet1 Recruits Janus Tyrosine Kinases and Signal Transducer and Activator of Transcription 3 and Stimulates Their Activities

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