Hormonal regulation of gluconeogenic gene transcription in the liver

Yabaluri, Nirmala; Bashyam, Murali D.

doi:10.1007/s12038-010-0052-0

Cited by 113 publications

(94 citation statements)

References 68 publications

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“…Since the liver is the major contributor of blood glucose, it is reasonable to hypothesize that the decrease in HIF1A protein levels in the liver under starvation underlie a liver adaption to a gluconeogenic state. 58 Hence our findings are consistent with a model in which CMA has an important role in starvation-induced liver metabolic stress.…”

Section: Discussionsupporting

confidence: 91%

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: Discussionsupporting

confidence: 91%

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

Fofo²,

et al. 2013

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“…To further confirm FoxO1 requirement for TH action, we performed ChIP-qPCR to analyze FoxO1 binding to the IRE located on the PCK1 and G6PC promoters, which has been shown earlier to be necessary for FoxO1-mediated transcription (9,27). ChIP-qPCR analyses showed that T 3 significantly increased FoxO1 binding to the IRE regions of PCK1 (Ϫ426 to Ϫ170) and G6PC (Ϫ237 to Ϫ70) promoters (Fig.…”

Section: T 3 Induction Of Pck1 and G6pc Mrna Expression Requires Foxomentioning

confidence: 79%

FoxO1 Deacetylation Regulates Thyroid Hormone-induced Transcription of Key Hepatic Gluconeogenic Genes

Singh

Sinha

Zhou

et al. 2013

Journal of Biological Chemistry

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Background: Thyroid hormone (TH) is known to induce transcription of hepatic gluconeogenic genes. Results: TH stimulates FoxO1 deacetylation to increase PCK1 and G6PC transcription. Conclusion: FoxO1 deacetylation by SirT1 is crucial for TH induction of its target genes, PCK1 and G6PC. Significance: This study demonstrates a novel role of FoxO1 in TH-mediated transcription that may explain some of the pleiotropic actions by TH.

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“…After the activation of PI3k/Akt/mTOR pathway, the expression of G6Pase and PEPCK is reduced, thereby decreasing hepatic glucose production (Yabaluri & Bashyam, 2010). Akt and mTOR (mTORC1 and mTORC2 subtypes) are the downstream genes of PI3k, but their relation is complex.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that the glucose metabolism can be regulated by insulin through the PI3K signal transduction cascade (Saltiel & Kahn, 2001). When this pathway is activated, the expression of G6Pase and PEPCK is reduced, thereby decreasing hepatic glucose production (O'Brien et al, 2001;Yabaluri & Bashyam, 2010). Akt, as a major cellular transduction element downstream PI3K, is a member of the insulin signaling pathway (Saltiel & Kahn, 2001).…”

Section: Introductionmentioning

confidence: 99%