Novel structure of the human GDNF gene

Woodbury, Dale; Schaar, Dale; Ramakrishnan, Lakshmi; Black, Ira B.

doi:10.1016/s0006-8993(98)00627-1

Cited by 37 publications

(41 citation statements)

References 27 publications

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“…Having in mind evidences that the transcription factor nuclear factor-kB (NF-kB) can regulate GDNF expression (Woodbury et al, 1998;Baecker et al, 1999;Tanaka et al, 2000), the effect of proinflammatory agents on GDNF expression is in agreement with the fact that IL-1b, TNF-a, and LPS activate NF-kB (Moynagh et al, 1993;Xie et al, 1994;Diehl et al, 1995). Moreover, NF-kB-DNA binding increases in U-87MG glioblastoma cells upon IL-1b treatment whereas dexamethasone significantly represses GDNF release .…”

Section: Inflammatory Signals and Gdnf Expressionmentioning

confidence: 55%

“…FGF-2 enhances the activity of the GDNF promoter (Grimm et al, 1998). The enhancement of GDNF expression by FGF-2 can occur through a consensus cAMP response element (CRE) sequence present within the GDNF promoter (Woodbury et al, 1998;Baecker et al, 1999) since FGF-dependent gene activation requires CRE-2 (Tan et al, 1994), and FGF activates a CREB kinase (Tan et al, 1996).…”

Section: Dopamine Agonistsmentioning

confidence: 99%

“…In addition, melatonin, via the MT1 receptor, can activate the MAPK-ERK pathway (Witt-Enderby et al, 2000), which has been shown to upregulate the transcription of vascular endothelial growth factor via specificity protein (Sp)1 and activating protein (AP)-2 sites (Milanini et al, 1998). This is relevant as both Sp1 and AP-2 binding sites are present in the GDNF promoter (Woodbury et al, 1998;Baecker et al, 1999) thereby providing another means by which melatonin can induce GDNF up-regulation.…”

Section: Immunophilin Ligandsmentioning

confidence: 99%

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Driving GDNF expression: The green and the red traffic lights

Saavedra

Baltazar

Duarte

2008

Progress in Neurobiology

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Section: Inflammatory Signals and Gdnf Expressionmentioning

confidence: 55%

Section: Dopamine Agonistsmentioning

confidence: 99%

Section: Immunophilin Ligandsmentioning

confidence: 99%

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Driving GDNF expression: The green and the red traffic lights

Saavedra

Baltazar

Duarte

2008

Progress in Neurobiology

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“…It can be induced by diverse extracellular stimuli Castro et al, 2005), and multiple transcription factor binding sites have been identified in the promoter sequence of the GDNF gene (Woodbury et al, 1998), such as cAMP response element (CRE) binding protein (CREB) (Matsushita et al, 1997; Baecker et al, 1999). Previous studies showed that CREB activation is associated with GDNF expression (Young et al, 1999;Lenhard et al, 2002), implying that CREB may participate in regulating GDNF expression as a transcriptional factor.…”

Section: Introductionmentioning

confidence: 99%

“…These results demonstrated that CREB-dependent transcriptional regulation is responsible for the GDNF-inducing properties of Leu-Ile. Although GDNF expression likely involves combinatorial interactions with multiple transcription factors including CREB, nuclear factor B (NF-B), and AP-2 (Woodbury et al, 1998), Leu-Ile-induced CREB activation is sufficient for inducing GDNF expression, indicating that CREB functions as an important transcriptional factor for the GDNF gene. Similarly, FK960 induces GDNF expression in CREB-dependent mechanisms (Koyama et al, 2004).…”

mentioning

confidence: 99%

An Analog of a Dipeptide-Like Structure of FK506 Increases Glial Cell Line-Derived Neurotrophic Factor Expression through cAMP Response Element-Binding Protein Activated by Heat Shock Protein 90/Akt Signaling Pathway

Cen¹,

Nitta²,

Ohya³

et al. 2006

J. Neurosci.

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Glial cell line-derived neurotrophic factor (GDNF) is an important neurotrophic factor that has therapeutic implications for neurodegenerative disorders. We previously showed that leucine-isoleucine (Leu-Ile), an analog of a dipeptide-like structure of FK506 (tacrolimus), induces GDNF expression both in vivo and in vitro. In this investigation, we sought to clarify the cellular mechanisms underlying the GDNF-inducing effect of this dipeptide. Leu-Ile transport was investigated using fluorescein isothiocyanate-Leu-Ile in cultured neurons, and the results showed the transmembrane mobility of this dipeptide. By liquid chromatography-mass spectrometry and quartz crystal microbalance assay, we identified heat shock cognate protein 70 as a protein binding specifically to Leu-Ile, and molecular modeling showed that the ATPase domain is the predicted binding site. Leu-Ile stimulated Akt phosphorylation, which was attenuated significantly by heat shock protein 90 (Hsp90) inhibitor geldanamycin (GA). Moreover, enhanced interaction between phosphorylated Akt and Hsp90 was detected by immunoprecipitation. Leu-Ile elicited an increase in cAMP response element binding protein (CREB) phosphorylation, which was inhibited by GA, indicating that CREB is a downstream target of Hsp90/Akt signaling. Leu-Ile elevated the levels of GDNF mRNA and protein expression, whereas inhibition of CREB blocked such effects. Leu-Ile promoted the binding activity of phosphorylated CREB with cAMP response element. These findings show that CREB plays a key role in transcriptional regulation of GDNF expression induced by Leu-Ile. In conclusion, Leu-Ile activates Hsp90/Akt/CREB signaling, which contributes to the upregulation of GDNF expression. It may represent a novel lead compound for the treatment of dopaminergic neurons or motoneuron diseases.

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Differential regulation of glial cell line-derived neurotrophic factor (GDNF) expression in human neuroblastoma and glioblastoma cell lines

Verity¹,

Wyatt²,

Lee³

et al. 1999

J. Neurosci. Res.

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Human SK-N-AS neuroblastoma and U-87MG glioblastoma cell lines were found to secrete relatively high levels of glial cell line-derived neurotrophic factor (GDNF). In response to growth factors, cytokines, and pharmacophores, the two cell lines differentially regulated GDNF release. A 24-hr exposure to tumor necrosis factor-alpha (TNFalpha; 10 ng/ml) or interleukin-1beta (IL-1,; 10 ng/ml) induced GDNF release in U-87MG cells, but repressed GDNF release from SK-N-AS cells. Fibroblast growth factors (FGF)-1, -2, and -9 (50 ng/ml), the prostaglandins PGA2, PGE2, and PGI2 (10 microM), phorbol 12,13-didecanoate (PDD; 10 nM), okadaic acid (10 nM), dexamethasone (1 microM), and vitamin D3 (1 microm) also differentially effected GDNF release from U-87MG and SK-N-AS cells. A result shared by both cell lines, was a two- to threefold increase in GDNF release by db-cAMP (1 mM), or forskolin (10 microM). In general, analysis of steady-state GDNF mRNA levels correlated with changes in extracellular GDNF levels in U-87MG cells but remained static in SK-N-AS cells. The data suggest that human GDNF synthesis/release can be regulated by numerous factors, signaling through multiple and diverse secondary messenger systems. Furthermore, we provide evidence of differential regulation of human GDNF synthesis/release in cells of glial (U-87MG) and neuronal (SK-N-AS) origin.

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Novel structure of the human GDNF gene

Cited by 37 publications

References 27 publications

Driving GDNF expression: The green and the red traffic lights

Driving GDNF expression: The green and the red traffic lights

An Analog of a Dipeptide-Like Structure of FK506 Increases Glial Cell Line-Derived Neurotrophic Factor Expression through cAMP Response Element-Binding Protein Activated by Heat Shock Protein 90/Akt Signaling Pathway

Differential regulation of glial cell line-derived neurotrophic factor (GDNF) expression in human neuroblastoma and glioblastoma cell lines

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