CREB mediates the cAMP-responsiveness of the tyrosine hydroxylase gene: use of an antisense RNA strategy to produce CREB-deficient PC12 cell lines

Piech-Dumas, Kristen M.; Tank, A. William

doi:10.1016/s0169-328x(99)00149-7

Cited by 49 publications

(48 citation statements)

References 28 publications

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“…CREB, ATF-1, and CREM (2-6). Among these transcription factors, only CREB was shown to be an activator of the TH gene transcription (7)(8)(9)(10). Our data confirmed that CREB is one of the TH-CRE-binding proteins in PC12D cells (Fig.…”

Section: Discussionsupporting

confidence: 82%

“…CREB, ATF-1, and CREM were shown to recognize the cAMP-responsive element (CRE) located at position Ϫ45/Ϫ38 in the TH promoter (2)(3)(4)(5)(6). CREB was reported to mediate basal and cAMP-induced TH transcription in various cultured cells including PC12 cells by the use of dominant-negative CREB protein and antisense RNA against CREB (7)(8)(9)(10). CREB is activated by phosphorylation on Ser 133 (11,12).…”

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confidence: 99%

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Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene

Suzuki

Yamakuni

Hagiwara

et al. 2002

Journal of Biological Chemistry

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Transcriptional regulation of catecholamine-synthesizing genes is important for the determination of neurotransmitters during brain development. We found that three catecholamine-synthesizing genes were transcriptionally up-regulated in cloned PC12D cells overexpressing V-1, a protein that is highly expressed during postnatal brain development (1). To reveal the molecular mechanism to regulate the expression of tyrosine hydroxylase (TH), which is the rate-limiting enzyme for catecholamine biosynthesis, we analyzed the transcription factors responsible for TH induction in the V-1 clonal cells. First, by using reporter constructs, we found that the transcription mediated by cAMP-responsive element (CRE) was selectively enhanced in the V-1 cells, and TH promoter activity was totally dependent on the CRE in the promoter region of the TH gene. Next, immunoblot analyses and a transactivation assay using a GAL4 reporter system revealed that ATF-2, but not cAMP-responsive element-binding protein (CREB), was highly phosphorylated and activated in the V-1 cells, while both CREB and ATF-2 were bound to the TH-CRE. Finally, the enhanced TH promoter activity was competitively attenuated by expression of a plasmid containing the ATF-2 transactivation domain. These data demonstrated that activation of ATF-2 resulted in the increased transcription of the TH gene and suggest that ATF-2 may be deeply involved in the transcriptional regulation of catecholamine-synthesizing genes during neural development.Catecholamines are synthesized from L-tyrosine by the sequential action of four enzymes: tyrosine is converted to DOPA by tyrosine hydroxylase (TH), 1 DOPA to dopamine by aromatic L-amino acid decarboxylase (AADC), dopamine to norepinephrine by dopamine ␤-hydroxylase (DBH), and norepinephrine to epinephrine by phenylethanolamine N-methyltransferase. The regulation of the gene expression of these enzymes is important for the determination of the expression of neurotransmitters during brain development as well as for brain function under physiological and pathological conditions. TH is the rate-limiting enzyme for catecholamine biosynthesis. The transcriptional regulation of the TH gene has been extensively studied, and many transcription factors were suggested to regulate TH gene expression. CREB, ATF-1, and CREM were shown to recognize the cAMP-responsive element (CRE) located at position Ϫ45/Ϫ38 in the TH promoter (2-6). CREB was reported to mediate basal and cAMP-induced TH transcription in various cultured cells including PC12 cells by the use of dominant-negative CREB protein and antisense RNA against CREB (7-10). CREB is activated by phosphorylation on Ser 133 (11,12). The activation of CREB by phosphorylation has been shown to mediate PKA-dependent (7, 13-15) and -independent (13, 14) induction of TH transcription. Functional and physiological roles of ATF-1 and CREM for TH transcription remained unclear. AP-1 transcription factors bound to the TPA-responsive element located at Ϫ205/Ϫ199 in the TH promoter, which also plays ...

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Section: Discussionsupporting

confidence: 82%

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confidence: 99%

Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene

Suzuki

Yamakuni

Hagiwara

et al. 2002

Journal of Biological Chemistry

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“…It is known that activation of the TrkB receptor leads to an increase in cAMP response element-binding protein (CREB) (Feng et al, 1999;Pizzorusso et al, 2000), which in turn regulates the expression of TH (Kim et al, 1993;LaneLadd et al, 1997;Piech-Dumas and Tank, 1999). Our results suggest that in addition to this pathway, activation of TrkB receptor by BDNF may regulate the expression of Phox2a.…”

Section: Discussionmentioning

confidence: 51%

Crucial role of TrkB ligands in the survival and phenotypic differentiation of developing locus coeruleus noradrenergic neurons

et al. 2003

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The role of glial cell-line derived neurotrophic factor (GDNF) and neurotrophins in the development of locus coeruleus noradrenergic neurons was evaluated. We found that two neurotrophic factors previously reported to prevent the degeneration of lesioned adult central noradrenergic neurons, GDNF and neurotrophin 3 (NT3), do not play significant roles in the prenatal development of locus coeruleus noradrenergic neurons, as demonstrated by: (1)the lack of alterations in double Gdnf/Nt3 null mutant mice;and (2) the lack of survival-promoting effects of GDNF and/or NT3 in rat E13.5 primary cultures. In contrast, null mutant mice for TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor and neurotrophin 4, displayed a clear loss of locus coeruleus noradrenergic neurons. In accordance with this,treatment of rat E13.5 primary cultures with TrkB ligands prevented the early loss of noradrenergic neurons and maintained their survival for up to 6 days in vitro. Moreover, an additional 5-10-fold increase in the number of tyrosine hydroxylase positive noradrenergic neurons was detected after 12 hours in culture. This second effect of TrkB ligands involved neither proliferation nor survival, because the number of BrdU- or TUNEL-positive noradrenergic neurons did not change and the effect was elicited by delayed administration of either factor. Because TrkB ligands increased the number of tyrosine hydroxylase-positive cells expressing Phox2a, a paired homeodomain protein required for the development of locus coeruleus noradrenergic neurons, but did not affect the number of Phox2a-positive tyrosine hydroxylase-negative cells,our results suggest that the second effect of TrkB ligands may involve promoting or inducing a noradrenergic phenotype. In summary, our findings suggest that, unlike NT3 and GDNF, TrkB ligands are required and sufficient to promote the development of central noradrenergic neurons.

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“…For example, in the pineal gland, ICER is involved in the repression of melatonin synthesis during the course of normal circadian rhythm (Foulkes et al, 1996) and is involved in the desensitization of thyroid-stimulating hormone and follicle-stimulating hormone receptors in the pituitary and Sertoli cells, respectively (Lalli and Sassone-Corsi, 1995;Monaco et al, 1995). In pheochromocytoma PC12 cells, ICER inhibits PKA-stimulated transcriptional activity of tyrosine hydroxylase (Piech-Dumas and Tank, 1999). ICER has also been implicated in the regulation of ACTH secretion from a pituitary-derived corticotroph cell line (Lamas et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Role of Glucocorticoids and cAMP-Mediated Repression in Limiting Corticotropin-Releasing Hormone Transcription during Stress

Shepard¹,

Liu²,

Sassone–Corsi³

et al. 2005

J. Neurosci.

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The role of glucocorticoids and the repressor isoform of cAMP response element (CRE) modulator (CREM), inducible cAMP early repressor (ICER), in limiting corticotropin-releasing hormone (CRH) transcription during restraint stress were examined in both intact and adrenalectomized rats receiving glucocorticoid replacement. CRH primary transcript, measured by intronic in situ hybridization, increased after 30 min of restraint and returned to basal levels by 90 min, despite the persistent stressor. The decline was independent of circulating glucocorticoids, because adrenalectomized rats displayed an identical pattern. ICER mRNA in the hypothalamic paraventricular nucleus (PVN) increased after 30 min and remained elevated for up to 4 h in a glucocorticoid-independent manner. Western blot and electrophoretic mobility shift assay analyses showed increases in endogenous ICER in the PVN of rats subjected to restraint stress for 3 h. Chromatin immunoprecipitation assays showed the recruitment of CREM by the CRH CRE in conjunction with decreases in RNA polymerase II (Pol II) binding in the PVN region of rats restrained for 3 h. These data show that stress-induced glucocorticoids do not mediate the limitation of CRH transcription. Furthermore, the ability of CREM to bind the CRH CRE and the time relationship between elevated CREM and reduced Pol II recruitment by the CRH promoter suggest that inhibitory isoforms of CREM induced during stress contribute to the decline in CRH gene transcription during persistent stimulation.

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CREB mediates the cAMP-responsiveness of the tyrosine hydroxylase gene: use of an antisense RNA strategy to produce CREB-deficient PC12 cell lines

Cited by 49 publications

References 28 publications

Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene

Identification of ATF-2 as a Transcriptional Regulator for the Tyrosine Hydroxylase Gene

Crucial role of TrkB ligands in the survival and phenotypic differentiation of developing locus coeruleus noradrenergic neurons

Role of Glucocorticoids and cAMP-Mediated Repression in Limiting Corticotropin-Releasing Hormone Transcription during Stress

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