Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid

Kido, Hiroshi; Fukusen, Naomi; Katunuma, Nobuhiko

doi:10.1021/bi00382a041

Cited by 24 publications

(6 citation statements)

References 23 publications

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“…Activation of PKC by treatment with TPA enhances the glucocorticoid-induced expression of liver tyrosine aminotransferase (TAT) (31,32). It was suggested that PKC may enhance glucocorticoid-induced TAT expression by facilitating the translocation of the glucocorticoid receptor (GR) to the nucleus (31).…”

Section: Discussionmentioning

confidence: 99%

Integration of hormone signaling in the regulation of human 25(OH)D₃24-hydroxylase transcription

Barletta

Dhawan

Christakos

2004

American Journal of Physiology-Endocrinology and Metabolism

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. In these cells, cotreatment with the PKC activator TPA and 1,25(OH)2D3 yielded a 27-fold increase in luciferase activity, which was 2-to 3-fold greater than activation obtained with 1,25(OH)2D3 alone (P Ͻ 0.05). Similar results were observed using LLCPK-1 kidney cells, suggesting that the previously observed enhancement of 1,25(OH)2D3-induced renal 24(OH)ase mRNA and activity by PKC activation occurs at the level of transcription. The functional cooperation between PKC activation and VDR was not found to be mediated by the AP-1 site in the h24(OH)ase promoter or by enhanced binding of GRIP or DRIP205 to VDR and was also not due to PKC-mediated phosphorylation of VDR on Ser 51 . Our study demonstrates that, in LLCPK-1 kidney cells, the PKC enhancement of 1,25(OH)2D3-stimulated transcription may be due, in part, to an increase in VDR concentration. In addition, inhibitors of the MAPK pathway were found to decrease the TPA enhancement (P Ͻ 0.05). Because activation of MAPK has been reported to result in the phosphorylation of SRC-1 and in functional cooperation between SRC-1 and CREB binding protein, we propose that the potentiation of VDR-mediated transcription may also be mediated through changes in the phosphorylation of specific VDR coregulators. , and the production of 1,24,25(OH) 3 D 3 is believed to be the initial step in the catabolism of 1,25(OH) 2 D 3 to calcitroic acid (46). Recent studies using the 24(OH)ase-null mutant mouse provided the first direct in vivo evidence that the C-24 pathway, initiated by the 24(OH)ase enzyme, is the major catabolic process that functions to regulate the physiological levels of 1,25(OH) 2 D 3 , thereby preventing the accumulation of toxic levels of the hormone (53). Thus 1,25(OH) 2 D 3 , by inducing the 24(OH)ase enzyme, stimulates its own deactivation.The cloning of the rat and human 24(OH)ase gene promoters has made possible, for the first time, studies related to the regulation of this major target of 1,25(OH) 2 D 3 action (7,30,39,59). The 24(OH)ase gene is the most transcriptionally responsive 1,25(OH) 2 D 3 -inducible gene identified to date. It is the first vitamin D-responsive gene to be controlled by two independent VDREs (7,30,59). Although a number of studies by us and others (4,13,14,22,45) have defined factors that affect rat 24(OH)ase transcription, very little work has been done to examine molecular mechanisms by which 1,25(OH) 2 D 3 and other factors affect the regulation of human 24(OH)ase transcription. In previous studies, two VDREs have been defined and a putative activating protein-1 (AP-1) site has been identified by sequence homology in the human

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Section: Discussionmentioning

confidence: 99%

Integration of hormone signaling in the regulation of human 25(OH)D₃24-hydroxylase transcription

Barletta

Dhawan

Christakos

2004

American Journal of Physiology-Endocrinology and Metabolism

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“…With glucocorticoids, phorbol esters enhanced hormone induction of hepatic enzymes (64), and inhibitors reduced this induction as well as nuclear translocation of the receptors (65). Protein kinase C activators, however, inhibited glucocorticoid-dependent transcription in NIH-3T3 cells (66).…”

Section: Effects Of Kinase Activators and Inhibitorsmentioning

confidence: 97%

Phosphorylation of Steroid Hormone Receptors*

1992

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Many observations with intact cells as well as cell-free systems suggest that receptors of the steroid hormone superfamily, along with other transcription factors, are regulated by phosphorylation. All receptors that have been analyzed carefully so far have turned out to be phosphoproteins. They are basally phosphorylated in the absence of ligand, and in many cases become hyperphosphorylated in the presence of hormone or other agonists, and sometimes of antagonists. Several studies indicate that hyperphosphorylation of receptors follows activation, and may require nuclear binding of the receptor. Serines are the predominant phosphorylated residues detected in receptors, with minor amounts of threonine. Tyrosine phosphorylation of the estrogen receptor is a subject of controversy. With various receptors, evidence has been found for phosphorylation in vivo of the N-terminal, hormone-binding, and DNA-binding domains, as well as of the hinge region. All but one of the phosphorylated sites identified in progesterone and glucocorticoid receptors by phosphopeptide mapping and sequencing are in the N-terminal domain; one is in the hinge region. Even after hormone treatment most of those sites are only partly phosphorylated, which means that several subpopulations of receptors, characterized by different states of phosphorylation and potentially different biological activities, must coexist. The majority of identified phosphorylated sites lie in consensus sequences for the PDPK. Many parallels can be discerned between phosphorylation of receptors and of other transcription factors. For example, several transcription factors become hyperphosphorylated on stimulation, and much indirect evidence points to regulation of both receptors and transcription factors by kinases and phosphatases, with cycling between different phosphorylated states. Functions of receptors that are regulated by phosphorylation are only beginning to be investigated. With transcription factors a substantial body of information is already available, and functions that appear to be thus regulated include dimerization, interactions with other proteins, binding to DNA, nuclear-cytoplasmic localization, and transcriptional activity. These and other functions may be found to be regulated by phosphorylation of receptors.

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“…TPA regulates gene transcription by phosphorylation of transcription factors AP-1 in a number of cases (Angel et al, 1987). The glucocorticoid dependence of the TPA induction of D-I1 might be due to an effect on the transcription of the D-I1 gene, as for hepatic tyrosine aminotransferase (Kido et al, 1987). The effect of TPA was transient, probably due to the loss of protein kinase C (Fishman et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

12‐O‐Tetradecanoylphorbol 13‐Acetate and Fibroblast Growth Factor Increase the 30‐kDa Substrate Binding Subunit of Type II Deiodinase in Astrocytes

Lennon

Esfandiari

Gavaret

et al. 1994

Journal of Neurochemistry

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Type II 5-deiodinase (D-ll) catalyzes the intracellular conversion of thyroxine (T, ) to 3,5,3'-triiodothyronine (T, ) in the brain. The D-ll activity in astroglial cell cultures is induced by several pathways including cyclic AMP (CAMP), 12-O-tetradecanoylphorbol 13-acetate (TPA), and fibroblast growth factors (FGFs). We have examined the effect of TPA and FGFs on the 30-kDa substrate binding subunit of D-11, by affinity labeling with N-bromoacetyl-['251]T4 in astroglial cells. TPA (0.1 pM), 20 ng/ml acidic FGF (aFGF), and 1 mM 8-bromo cyclic AMP all caused an increase in the 30-kDa protein. cAMP induced the greatest increase (fivefold) followed by TPA (3.2-fold) and FGF (2.8-fold). Glucocorticoids acted synergistically with cAMP and aFGF and promoted the effect of TPA. Affinity labeling was competitively inhibited by bromoacetyl-T, > bromoacetyl-T, > T , > reverse T, > iopanoic acid > T, > 3,5,3'-triiodothyroacetic acid. The effect of TPA (0.1 p M ) was maximum at 8 h and then gradually decreased. aFGF (20 ng/ml) plus heparin (17 pg/ml) induced a maximal 30-kDa increase at 8 h, which stayed stable for up to 24 h. The effect of aFGF was concentration dependent. Of the other growth factors studied, only basic FGF and platelet-derived growth factor induced small increases in the 30-kDa protein. Epidermal growth factor had little effect. In vitro labeling of CAMP, TPA, and aFGF-stimulated cell sonicates resulted in an increase in the 30-kDa protein that paralleled the increase in D-ll activity. These results correlate well with our previous studies showing that several distinct signaling pathways regulate D-ll activity. They suggest that the regulation of D-ll in astrocytes by CAMP, TPA, and aFGF involves an accumulation of the 30-kDa substrate binding subunit. Key Words: Type II 5'-deiodinase-Thyroxine-3,5,3'-Triiodothyronine-Astrocyte-Brain-Cyclic AMP-12-O-Tetradecanoylphorbol13-acetate-Fibroblast growth factor.

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Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid

Cited by 24 publications

References 23 publications

Integration of hormone signaling in the regulation of human 25(OH)D₃24-hydroxylase transcription

Integration of hormone signaling in the regulation of human 25(OH)D₃24-hydroxylase transcription

Phosphorylation of Steroid Hormone Receptors*

12‐O‐Tetradecanoylphorbol 13‐Acetate and Fibroblast Growth Factor Increase the 30‐kDa Substrate Binding Subunit of Type II Deiodinase in Astrocytes

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Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid

Cited by 24 publications

References 23 publications

Integration of hormone signaling in the regulation of human 25(OH)D324-hydroxylase transcription

Integration of hormone signaling in the regulation of human 25(OH)D324-hydroxylase transcription

Phosphorylation of Steroid Hormone Receptors*

12‐O‐Tetradecanoylphorbol 13‐Acetate and Fibroblast Growth Factor Increase the 30‐kDa Substrate Binding Subunit of Type II Deiodinase in Astrocytes

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Integration of hormone signaling in the regulation of human 25(OH)D₃24-hydroxylase transcription

Integration of hormone signaling in the regulation of human 25(OH)D₃24-hydroxylase transcription