The Transcription Factors HIF-1 and HNF-4 and the Coactivator p300 Are Involved in Insulin-regulated Glucokinase Gene Expression via the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway

Roth, Ulrike; Curth, Katja; Unterman, Terry G.; Kietzmann, Thomas

doi:10.1074/jbc.m308391200

Cited by 104 publications

(89 citation statements)

References 65 publications

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“…53 Many of these genes lead to increased glucose uptake [54][55][56] and glycolysis. 57 In this context HIF1A, by activating the expression of numerous glycolysis-related genes, as well as by increasing the expression of proteins that help cells capture blood glucose, is an inducer of glycolysis.…”

Section: Discussionmentioning

confidence: 99%

STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy

Fofo²,

et al. 2013

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The transcription factor hiF1 is mostly regulated by the oxygen-dependent proteasomal degradation of the labile subunit hiF1A. recent data showed degradation of hiF1A in the lysosome through chaperone-mediated autophagy (cMA). however the molecular mechanism involved has not been elucidated. This study shows that the KFerQ-like motif, that has been identified in all cMA substrates, is required to mediate the interaction between hiF1A and the chaperone hSpA8. Moreover, mutations in the KFerQ-like motif of hiF1A preclude the interaction with the cMA receptor LAMp2A, thus inhibiting its lysosomal degradation. importantly, we show for the first time that the ubiquitin ligase STUB1 is required for degradation of hiF1A in the lysosome by cMA. indeed, mutations in STUB1 that inhibit either the ubiquitin ligase activity or its ability to bind to hSpA8, both prevent degradation of hiF1A by cMA. Moreover, we show that hiF1A binds to and is translocated into intact lysosomes isolated from rat livers. This new pathway for degradation of hiF1A does not depend on the presence of oxygen and is activated in response to nutrient deprivation such that the levels of hiF1A bound to cMA positive lysosomes significantly increase in starved animal livers and the binding of hiF1A to LAMp2A increases in response to serum deprivation. Moreover, excessive degradation of hiF1A by cMA compromises cells' ability to respond to and survive under hypoxia, suggesting that this pathway might be of pathophysiological importance in conditions that combine hypoxia with starvation. leucinylleucinylleucinal/proteasome inhibitor; MTT, 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; RCC, renal cell carcinoma; Serpinb, serpin peptidase inhibitor, clade B/Ovalbumin; SLC2A1, solute carrier family 2 (facilitated glucose transporter)/glucose transporter; STUB1, STIP1 homology and U-box containing protein 1; TPR, tetratricopeptide repeat; UPS, ubiquitin-proteasome system; VEGFA, vascular endothelial growth factor A; u-box, modified RING finger domain lacking the metal-chelating residues

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Section: Discussionmentioning

confidence: 99%

STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy

Fofo²,

et al. 2013

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“…Thus, the difference in modes of action of wortmannin in mammals and plants may relate to the more complicated role that the TGN/PCR plays in plant cells. Despite the many caveats in working with wortmannin (Roth et al, 2004), which also probably apply to plants, it will be interesting to determine whether the effects of wortmannin as described here in tobacco BY-2 cells can be confirmed in other plant cells. Indeed, an endosome as defined by labeling with At SNX1-GFP in Arabidopsis cells was recently shown to form small vacuoles in response to wortmannin treatment (Jaillais et al, 2006).…”

Section: Wortmannin Targets Both Early and Late Endosomes (Pvc) In Tomentioning

confidence: 99%

“…It would seem that whereas the internalization of PM receptors continues, or may even be increased, in the presence of wortmannin, receptor recycling or the further transport of receptors down the degradative pathway is inhibited (Roth et al, 2004). In addition to being present on multivesicular late endosomes, the substrate for PI-3K, PI3P, is also found on early endosomes (Rubino et al, 2000).…”

Section: Wortmannin Targets Both Early and Late Endosomes (Pvc) In Tomentioning

confidence: 99%

Rice SCAMP1 Defines Clathrin-Coated,trans-Golgi–Located Tubular-Vesicular Structures as an Early Endosome in Tobacco BY-2 Cells

et al. 2007

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We recently identified multivesicular bodies (MVBs) as prevacuolar compartments (PVCs) in the secretory and endocytic pathways to the lytic vacuole in tobacco (Nicotiana tabacum) BY-2 cells. Secretory carrier membrane proteins (SCAMPs) are post-Golgi, integral membrane proteins mediating endocytosis in animal cells. To define the endocytic pathway in plants, we cloned the rice (Oryza sativa) homolog of animal SCAMP1 and generated transgenic tobacco BY-2 cells expressing yellow fluorescent protein (YFP)-SCAMP1 or SCAMP1-YFP fusions. Confocal immunofluorescence and immunogold electron microscopy studies demonstrated that YFP-SCAMP1 fusions and native SCAMP1 localize to the plasma membrane and mobile structures in the cytoplasm of transgenic BY-2 cells. Drug treatments and confocal immunofluorescence studies demonstrated that the punctate cytosolic organelles labeled by YFP-SCAMP1 or SCAMP1 were distinct from the Golgi apparatus and PVCs. SCAMP1-labeled organelles may represent an early endosome because the internalized endocytic markers FM4-64 and AM4-64 reached these organelles before PVCs. In addition, wortmannin caused the redistribution of SCAMP1 from the early endosomes to PVCs, probably as a result of fusions between the two compartments. Immunogold electron microscopy with high-pressure frozen/freeze-substituted samples identified the SCAMP1-positive organelles as tubular-vesicular structures at the trans-Golgi with clathrin coats. These early endosomal compartments resemble the previously described partially coated reticulum and trans-Golgi network in plant cells.

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“…by modulating the function of FoxO1 and its interaction with HNF-4). Previously, we reported that HNF-4 plays an important role in stimulating the FoxO1 Regulates Glucokinase expression of GK in the liver and that an HNF-4 binding site in the proximal GK promoter is required for this effect (9). Previous studies also have shown that interaction between FoxO1 and HNF-4 disturbs HNF-4 function both by impairing its ability to bind to HNF-4 response elements (14) and by disrupting the function of the HNF-4 transactivation domain (64).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies indicate that several transcription factors, including USF-1 and -2 (upstream stimulatory factor-1 and -2) (7,8), HIF-1 (hypoxia-inducible factor-1) (9), PPAR␥ (peroxisome proliferator-activated receptor-␥) (10), sterol regulatory element binding protein-1c (11,12), and hepatocyte nuclear factor-4␣ (HNF-4␣) (13) may contribute to liver GK expression. We have reported that HNF-4 contributes to the effect of insulin on GK induction through a phosphatidylinositol 3Ј-kinase/protein kinase B-dependent mechanism (9). HNF-4 has been shown to interact with FoxO1 (14), an insulin-responsive transcription factor (15), suggesting the possibility that interactions between FoxO1 and HNF-4 may contribute to the regulation of GK expression.…”

mentioning

confidence: 98%

FOXO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression by Resveratrol

Kietzmann¹,

Ganjam²,

Dimova³

2010

Z Gastroenterol

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Resveratrol, a polyphenol derived from grapes, exerts important effects on glucose and lipid metabolism, yet detailed mechanisms mediating these effects remain unknown. The liver plays a central role in energy homeostasis, and glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and that HNF-4 can stimulate GK expression in the liver. Here, we examined the role of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression. Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes, and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel shift, supershift assay, and chromatin immunoprecipitation studies show that FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4 within the GK promoter is essential for mediating the effects of resveratrol. Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to its binding site, and knockdown of FoxO1 blocks this effect of resveratrol. Coprecipitation and chromatin immunoprecipitation studies show that resveratrol enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner. These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol.The liver is a key organ in energy homeostasis, and glucokinase (GK) 3 plays a major role in promoting hepatic glucose utilization and maintenance of blood glucose homeostasis.Compared with other hexokinases, GK has a smaller molecular mass (100 versus 52 kDa, respectively) and a lower affinity for glucose, with an S 0.5 for glucose in the range of about 7-8 mmol/liter. Although GK binds to a regulatory protein (GKRP) and exists as a monomer, it displays sigmoidal kinetics with a Hill coefficient of about 1.5-1.7, indicating cooperativity with its substrate, glucose (1-3). These characteristics allow GK to react with glucose across the range of physiological glucose concentrations reached in vivo. Although GK is expressed predominantly in hepatocytes and pancreatic ␤-cells, it also is expressed in some neuroendocrine cells of the gastrointestinal tract and the brain, where it also may contribute to glucose sensing (4).In the liver, GK is expressed predominantly in the less aerobic perivenous zone (5), and its expression is stimulated by insulin (6). Previous studies indicate that several transcription factors, including USF-1 and -2 (upstream stimulatory factor-1 and -2) (7, 8), HIF-1 (hypoxia-inducible factor-1) (9), PPAR␥ (peroxisome proliferator-activated receptor-␥) (10), sterol regulatory element binding protein-1c (11,12), and hepatocyte nuclear factor-4␣ (HNF-4␣) (...

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The Transcription Factors HIF-1 and HNF-4 and the Coactivator p300 Are Involved in Insulin-regulated Glucokinase Gene Expression via the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway

Cited by 104 publications

References 65 publications

STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy

STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy

Rice SCAMP1 Defines Clathrin-Coated,trans-Golgi–Located Tubular-Vesicular Structures as an Early Endosome in Tobacco BY-2 Cells

FOXO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression by Resveratrol

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