GLI Activates Transcription through a Herpes Simplex Viral Protein 16-Like Activation Domain

Yoon, Joon Won; Liu, Cheng Z.; Yang, Jian; Swart, Rachel; Iannaccone, Philip M.; Walterhouse, David

doi:10.1074/jbc.273.6.3496

Cited by 88 publications

(86 citation statements)

References 33 publications

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“…As previously reported, the N-terminal region (Gli1D1-176) was dispensable for transcriptional activation in this assay, while the C-terminal region (Gli1D1020-1111) containing the Gli1 activation domain was required for activation (Yoon et al, 1998). Deletion of a small portion of the zinc finger region (Gli1D1-243) also greatly reduced the activation of the Gli reporter.…”

Section: Multiple Domains Of Gli1 Are Required For Inhibition Of Myodsupporting

confidence: 81%

The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation

et al. 2006

Oncogene

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Section: Multiple Domains Of Gli1 Are Required For Inhibition Of Myodsupporting

confidence: 81%

The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation

et al. 2006

Oncogene

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“…Another question concerns the interaction of AR 16)36 with other proteins. One candidate might be the TFIID TATA box-binding protein associated factor 31, TAF II 31, which has been found to interact with FxxFF motifs in acidic transcription activation domains of p65 (nuclear factor-kappa B), VP16, p53 and related proteins [31,[49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Amino acids 3–13 and amino acids in and flanking the ²³FxxLF²⁷ motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Steketee

Berrevoets

Dubbink

et al. 2002

European Journal of Biochemistry

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The N-terminal domain (NTD) and the ligand-binding domain (LBD) of the androgen receptor (AR) exhibit a ligand-dependent interaction (N/C interaction). Amino acids 3-36 in the NTD (AR 3)36 ) play a dominant role in this interaction. Previously, it has been shown that a FxxFF motif in AR 3)36 , 23 FxxLF 27 , is essential for LBD interaction. We demonstrate in the current study that AR 3)36 can be subdivided into two functionally distinct fragments: AR 3)13 and AR 16)36 . AR 3)13 does not directly interact with the AR LBD, but rather contributes to the transactivation function of the AR.NTD-AR.LBD complex. AR 16)36, encompassing the 23 FxxLF 27 motif, is predicted to fold into a long amphipathic a-helix. A second FxxFF candidate protein interaction motif within the helical structure, 30 VREVI 34 , shows no affinity to the LBD. Within AR 16)36 , amino acid residues in and flanking the 23 FxxLF 27 motif are demonstrated to modulate N/C interaction. Substitution of Q24 and N25 by alanine residues enhances N/C interaction. Substitution of amino acids flanking the 23 FxxLF 27 motif by alanines are inhibitory to LBD interaction.

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“…SHH signaling is mediated by the GLI family of transcription factors (10). One of these genes, GLI1, has been shown to be a transcriptional activator operating through a C-terminal VP-16-like acidic helical domain (11). GLI1 transforms cells in culture, and its expression is associated with significant human cancers including basal cell carcinoma (12), medulloblastoma (13), and sarcomas (14).…”

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confidence: 99%

Gene Expression Profiling Leads to Identification of GLI1-binding Elements in Target Genes and a Role for Multiple Downstream Pathways in GLI1-induced Cell Transformation

Yoon¹,

Kita²,

Frank³

et al. 2002

Journal of Biological Chemistry

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296

277

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The zinc finger transcription factor GLI1, which mediates Sonic hedgehog signaling during development, is expressed in several human cancers, including basal cell carcinoma, medulloblastoma, and sarcomas. We identified 147 genes whose levels of expression were significantly altered in RNA obtained from cells demonstrating a transformed phenotype with stable GLI1 expression or stable Ha-ras expression. Comparison of expression profiles from GLI1-and Ha-ras-expressing cells established a set of genes unique to GLI1-induced cell transformation. Thirty genes were altered by stable GLI1 expression, and 124 genes were changed by stable Ha-ras expression. Seven genes had altered expression levels in both GLI1-and Ha-ras-expressing cells. Genes whose expression was altered by GLI1 included cell cycle genes, cell adhesion genes, signal transduction genes, and genes regulating apoptosis. GLI1 consensus DNA-binding sequences were identified in the 5 regions of cyclin D2, IGFBP-6, osteopontin, and plakoglobin, suggesting that these genes represent immediate downstream targets. Gel shift analysis confirmed the ability of the GLI1 protein to bind these sequences. Up-regulation of cyclin D2 and down-regulation of plakoglobin were demonstrated in GLI1-amplified compared with non-amplified human rhabdomyosarcoma cells. Many of the GLI1 targets with known function identified in this study increase cell proliferation, indicating that GLI1-induced cell transformation occurs through multiple downstream pathways.Important gene hierarchies, in part coding for components of signal transduction pathways, regulate growth and differentiation during development. One such pathway is the Sonic hedgehog-Patched-Gli pathway (1). SHH 1 signaling is critical to the genetic specification of fate of many tissues during early organogenesis including the central nervous system (2, 3), lung (4), prostate (5), bone (6 -8), and muscle (9). SHH signaling is mediated by the GLI family of transcription factors (10). One of these genes, GLI1, has been shown to be a transcriptional activator operating through a C-terminal VP-16-like acidic helical domain (11). GLI1 transforms cells in culture, and its expression is associated with significant human cancers including basal cell carcinoma (12), medulloblastoma (13), and sarcomas (14). Few downstream targets of GLI1 are known, which precludes a clear understanding of its action in carcinogenesis. Genetic evidence suggests that PTCH and Wnt genes are downstream targets of GLI1 (15), and biochemical evidence has established HNF-3␤ (Hepatocyte Nuclear Factor-3␤) as a target of GLI1 during development (16).Microarray technology has provided a methodology to study the expression of thousands of genes simultaneously and has been used in many important settings (17). Among these is the dissection of signal transduction pathways. To identify unique downstream targets of GLI1, we have utilized a cell transformation phenotype as a selection system for the stable integration and expression of either GLI1 or Ha-ras in RK3...

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GLI Activates Transcription through a Herpes Simplex Viral Protein 16-Like Activation Domain

Cited by 88 publications

References 33 publications

The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation

The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation

Amino acids 3–13 and amino acids in and flanking the ²³FxxLF²⁷ motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Gene Expression Profiling Leads to Identification of GLI1-binding Elements in Target Genes and a Role for Multiple Downstream Pathways in GLI1-induced Cell Transformation

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GLI Activates Transcription through a Herpes Simplex Viral Protein 16-Like Activation Domain

Cited by 88 publications

References 33 publications

The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation

The hedgehog regulated oncogenes Gli1 and Gli2 block myoblast differentiation by inhibiting MyoD-mediated transcriptional activation

Amino acids 3–13 and amino acids in and flanking the 23FxxLF27 motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Gene Expression Profiling Leads to Identification of GLI1-binding Elements in Target Genes and a Role for Multiple Downstream Pathways in GLI1-induced Cell Transformation

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Amino acids 3–13 and amino acids in and flanking the ²³FxxLF²⁷ motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor