General Information:

Id: 918
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mus musculus
article
Reference: Liu Y et al.(2008) A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 456: 269-273 [PMID: 18849969]

Interaction Information:

Comment In keeping with the decrease in gluconeogenic gene expression, hepatic CRTC2 protein amounts were downregulated in response to prolonged fasting.
Formal Description
Interaction-ID: 5552

environment

prolonged fasting

decreases_quantity of

gene/protein

CRTC2

in liver
Comment In keeping with the decrease in gluconeogenic gene expression, hepatic CRTC2 protein amounts were downregulated in response to prolonged fasting.
Formal Description
Interaction-ID: 5569

environment

prolonged fasting

decreases_activity of

process

gluconeogenesis

in liver
Comment Although undetectable in 6-h-fasted mice, ubiquitinated CRTC2 protein amounts increased after 18 h of fasting.
Formal Description
Interaction-ID: 5570

environment

prolonged fasting

increases_ubiquitination/sumoylation of

gene/protein

CRTC2

Comment Prolonged exposure to glucagon triggered CRTC2 degradation in primary hepatocytes; these effects were blocked by treatment with the proteasome inhibitor MG132 and by RNA interference (RNAi)-mediated depletion of COP1.
Formal Description
Interaction-ID: 5571

gene/protein

Glucagon

decreases_quantity of

gene/protein

CRTC2

in liver; via increased degradation of CRTC2
Comment Prolonged exposure to glucagon triggered CRTC2 degradation in primary hepatocytes; these effects were blocked by treatment with the proteasome inhibitor MG132 and by RNA interference (RNAi)-mediated depletion of COP1.
Formal Description
Interaction-ID: 5572

gene/protein

COP1

decreases_quantity of

gene/protein

CRTC2

in liver; via increased degradation of CRTC2
Comment Prolonged exposure to glucagon triggered CRTC2 degradation in primary hepatocytes; these effects were blocked by treatment with the proteasome inhibitor MG132 and by RNA interference (RNAi)-mediated depletion of COP1.
Formal Description
Interaction-ID: 5573

gene/protein

COP1

increases_ubiquitination/sumoylation of

gene/protein

CRTC2

in liver
Comment In contrast to CRTC2, hepatic FOXO1 protein levels remained constant during fasting, suggesting that these transcriptional regulators are differentially regulated.
Formal Description
Interaction-ID: 5574

environment

prolonged fasting

NOT affects_quantity of

gene/protein

FOXO1

in liver
Comment RNAi-mediated depletion of hepatic CRTC2 reduced the gluconeogenic profile, which includes Ad-G6Pase-luc activity, gluconeogenic gene expression, and circulating blood glucose concentrations in short-term fasted mice, whereas depletion of FOXO1 had only modest effects at this time. In contrast, FOXO1 knockdown substantially reduced the gluconeogenic profile after 18 h of fasting, when CRTC2 was degraded.
Formal Description
Interaction-ID: 5576

gene/protein

CRTC2

increases_activity of

process

gluconeogenesis

in liver; after short-term fasting
Comment RNAi-mediated depletion of hepatic CRTC2 reduced the gluconeogenic profile, which includes Ad-G6Pase-luc activity, gluconeogenic gene expression, and circulating blood glucose concentrations in short-term fasted mice, whereas depletion of FOXO1 had only modest effects at this time. In contrast, FOXO1 knockdown substantially reduced the gluconeogenic profile after 18 h of fasting, when CRTC2 was degraded.
Formal Description
Interaction-ID: 5577

gene/protein

FOXO1

increases_activity of

process

gluconeogenesis

in liver; after long-term fasting when CRTC2 is degraded
Comment Fasting led to CRTC2 acetylation after 8 h and to CRTC2 ubiquitination after 24 h.
Formal Description
Interaction-ID: 5581

environment

fasting for 8 h

increases_acetylation of

gene/protein

CRTC2

in liver
Comment Fasting led to CRTC2 acetylation after 8 h and to CRTC2 ubiquitination after 24 h.
Formal Description
Interaction-ID: 5586

environment

fasting for 24 h

increases_ubiquitination/sumoylation of

gene/protein

CRTC2

in liver
Comment Exposure of primary hepatocytes to glucagon triggered CRTC2 acetylation; this effect was reversed by subsequent exposure to insulin.
Formal Description
Interaction-ID: 5587

gene/protein

Glucagon

increases_acetylation of

gene/protein

CRTC2

in liver
Comment Exposure of primary hepatocytes to glucagon triggered CRTC2 acetylation; this effect was reversed by subsequent exposure to insulin.
Formal Description
Interaction-ID: 5589

complex/PPI

Insulin

decreases_acetylation of

gene/protein

CRTC2

in liver
Comment Short-term fasting increased the CRTC2-p300 interaction in liver, whereas long-term fasting disrupted it.
Formal Description
Interaction-ID: 5632

environment

short-term fasting

increases_quantity of

complex/PPI

CRTC2-EP300 complex

in liver
Comment Short-term fasting increased the CRTC2-p300 interaction in liver, whereas long-term fasting disrupted it.
Formal Description
Interaction-ID: 5633

environment

prolonged fasting

decreases_quantity of

complex/PPI

CRTC2-EP300 complex

in liver
Comment Exposure to glucagon or forskolin (FSK) triggered the association of CRTC2 and p300 in primary hepatocytes; these effects were blocked by subsequent exposure to insulin.
Formal Description
Interaction-ID: 5634

gene/protein

Glucagon

increases_quantity of

complex/PPI

CRTC2-EP300 complex

in liver
Comment Exposure to glucagon or forskolin (FSK) triggered the association of CRTC2 and p300 in primary hepatocytes; these effects were blocked by subsequent exposure to insulin.
Formal Description
Interaction-ID: 5637

drug/chemical compound

Coleonol

increases_quantity of

complex/PPI

CRTC2-EP300 complex

in liver
Comment Exposure to glucagon or forskolin (FSK) triggered the association of CRTC2 and p300 in primary hepatocytes; these effects were blocked by subsequent exposure to insulin.
Formal Description
Interaction-ID: 5639

complex/PPI

Insulin

decreases_quantity of

complex/PPI

CRTC2-EP300 complex

in liver
Comment p300 is activated by dephosphorylation at Ser 89 during fasting.
Formal Description
Interaction-ID: 5651

environment

fasting

decreases_phosphorylation of

gene/protein

EP300

at Ser89 of EP300
Comment p300 is activated by dephosphorylation at Ser 89 during fasting.
Formal Description
Interaction-ID: 5653

environment

fasting

increases_activity of

gene/protein

EP300

via dephosphorylation at Ser89 of EP300
Comment p300 increased hepatic CRTC2 activity by acetylating it at Lys 628.
Formal Description
Interaction-ID: 5654

gene/protein

EP300

increases_activity of

gene/protein

CRTC2

in liver; via acetylation at Lys628 of CRTC2
Comment p300 increased hepatic CRTC2 activity by acetylating it at Lys 628.
Formal Description
Interaction-ID: 5659

gene/protein

EP300

increases_acetylation of

gene/protein

CRTC2

in liver; at Lys628 of CRTC2
Comment Hepatic SIRT1 protein accumulated after 18 h of fasting, when CRTC2 acetylation and protein amounts were correspondingly reduced.
Formal Description
Interaction-ID: 5660

environment

prolonged fasting

increases_quantity of

gene/protein

SIRT1

in liver
Comment During prolonged fasting, SIRT1 deacetylates CRTC2 and promotes its ubiquitin-dependent degradation by COP1.
Formal Description
Interaction-ID: 5662

gene/protein

SIRT1

decreases_acetylation of

gene/protein

CRTC2

during prolonged fasting
Comment During prolonged fasting, SIRT1 deacetylates CRTC2 and promotes its ubiquitin-dependent degradation by COP1.
Formal Description
Interaction-ID: 5663

gene/protein

COP1

increases_ubiquitination/sumoylation of

gene/protein

CRTC2

during prolonged fasting
Comment During prolonged fasting, SIRT1 deacetylates CRTC2 and promotes its ubiquitin-dependent degradation by COP1.
Formal Description
Interaction-ID: 5666

gene/protein

COP1

decreases_quantity of

gene/protein

CRTC2

during prolonged fasting via increased degradation of CRTC2
Comment During prolonged fasting, SIRT1 deacetylates CRTC2 and promotes its ubiquitin-dependent degradation by COP1.
Formal Description
Interaction-ID: 5667

gene/protein

SIRT1

decreases_quantity of

gene/protein

CRTC2

via ubiquitin-dependent degradation by COP1 during prolonged fasting
Comment The reciprocal upregulation of FOXO1 activity by SIRT1 during prolonged fasting seems to be critical in maintaining energy balance through its effects on glucose metabolism.
Formal Description
Interaction-ID: 5669

gene/protein

SIRT1

increases_activity of

gene/protein

FOXO1

during prolonged fasting
Comment The reciprocal upregulation of FOXO1 activity by SIRT1 during prolonged fasting seems to be critical in maintaining energy balance through its effects on glucose metabolism.
Formal Description
Interaction-ID: 5671

gene/protein

FOXO1

affects_activity of

Comment Disrupting SIRT1 activity, by liver-specific knockout of the Sirt1 gene or by administration of a SIRT1 antagonist, increased CRTC2 activity and glucose output, whereas exposure to SIRT1 agonists reduced them.
Formal Description
Interaction-ID: 5673

gene/protein

SIRT1

affects_activity of

gene/protein

CRTC2

Comment Disrupting SIRT1 activity, by liver-specific knockout of the Sirt1 gene or by administration of a SIRT1 antagonist, increased CRTC2 activity and glucose output, whereas exposure to SIRT1 agonists reduced them.
Formal Description
Interaction-ID: 5727

gene/protein

SIRT1

affects_quantity of

drug/chemical compound

Glucose

Comment Disrupting SIRT1 activity, by liver-specific knockout of the Sirt1 gene or by administration of a SIRT1 antagonist, increased CRTC2 activity and glucose output, whereas exposure to SIRT1 agonists reduced them.
Formal Description
Interaction-ID: 5728

gene/protein

SIRT1

decreases_activity of

gene/protein

CRTC2