General Information:

Id: 6,387 (click here to show other Interactions for entry)
Diseases: Metabolic
Mammalia
review
Reference: Cetrullo S et al.(2015) mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management Crit. Rev. Eukaryot. Gene Expr. 25: 59-75 [PMID: 25955819]

Interaction Information:

Comment Sir2 hast seven orthologs (Sirt1-Sirt7) in mammals that are ubiquitously expressed in tissues and have different subcellular localizations and activities. While Sirt1, Sirt6, and Sirt7 lie mainly in the nucleus, Sirt3, Sirt4, and Sirt5 are mitochondrial protein and Sirt2 is found to act in the cytoplasm.
Formal Description
Interaction-ID: 61567

gene/protein

SIRT1

is localized in

cellular component

nucleus

Comment The NAD+ biosynthetic rate is crucial in Sirt1 regulation. Only in the presence of the cosubstrate NAD+ does the reaction lead to removal of actyl groups from an acetylated substrate, releasing nicotinamide, 2'-O-acetyl-ADP-ribose and the deacetylated target (e.g. histonic lysines).
Formal Description
Interaction-ID: 61617

drug/chemical compound

NAD+

affects_activity of

gene/protein

SIRT1

Comment Two studies have reported an interaction between Sirt1 and CLOCK-BMAL1, joint master regulators of the circadian clock, which implies that Sirt1 is the molcular link among several cellular processes, playing a regulatory role in the circadian clock, aging, cellular metabolism, and stress response. These different processes are characterized by changes in NAD+ levels and in turn influence Sirt1 activity in a fine and detailed circuit.
Formal Description
Interaction-ID: 61621

gene/protein

SIRT1

interacts (colocalizes) with

complex/PPI

CLOCK-BMAL1 complex

Comment It has been shown that NAD+ increases in mammals during exercise, fasting, and caloric restriction, and the same conditions are associated with intensive Sirt1 activity.
Formal Description
Interaction-ID: 61624

environment

exercise

increases_activity of

gene/protein

SIRT1

Comment It has been shown that NAD+ increases in mammals during exercise, fasting, and caloric restriction, and the same conditions are associated with intensive Sirt1 activity.
Formal Description
Interaction-ID: 61625

environment

fasting

increases_activity of

gene/protein

SIRT1

Comment It has been shown that NAD+ increases in mammals during exercise, fasting, and caloric restriction, and the same conditions are associated with intensive Sirt1 activity.
Formal Description
Interaction-ID: 61626

environment

caloric restriction

increases_activity of

gene/protein

SIRT1

Comment Two studies have reported an interaction between Sirt1 and CLOCK-BMAL1, joint master regulators of the circadian clock, which implies that Sirt1 is the molecular link among several cellular processes, playing a regulatory role in the circadian clock, aging, cellular metabolism, and stress response. These different processes are characterized by changes in NAD+ levels and in turn influence Sirt1 activity in a fine and detailed circuit.
Formal Description
Interaction-ID: 61630

gene/protein

SIRT1

affects_activity of

process

circadian clock

Comment Several signals converge on Sirt1 to stimulate its protein deacetylase activity, which uses NAD+ as a cosubstrate and releases acetyl-ADP-ribose and nicotinamide (NAM).
Formal Description
Interaction-ID: 61631

gene/protein

SIRT1

increases_quantity of

drug/chemical compound

O-Acetyl-ADP-ribose

Comment Several signals converge on Sirt1 to stimulate its protein deacetylase activity, which uses NAD+ as a cosubstrate and releases acetyl-ADP-ribose and nicotinamide (NAM).
Formal Description
Interaction-ID: 61632

gene/protein

SIRT1

increases_quantity of

drug/chemical compound

Nicotinamide

Drugbank entries Show/Hide entries for
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61635

gene/protein

SIRT1

affects_activity of

gene/protein

TP53

Drugbank entries Show/Hide entries for TP53
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61641

gene/protein

SIRT1

affects_activity of

gene/protein

PPARGC1A

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61642

gene/protein

SIRT1

affects_activity of

gene/protein

HIF1A

Drugbank entries Show/Hide entries for HIF1A
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61643

gene/protein

SIRT1

affects_activity of

gene/protein

EPAS1

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61644

gene/protein

SIRT1

affects_activity of

gene/protein

NR1H

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61645

gene/protein

SIRT1

affects_activity of

gene/protein

GPR85

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61646

gene/protein

SIRT1

affects_activity of

gene/protein

NR1H4

Drugbank entries Show/Hide entries for NR1H4
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61647

gene/protein

SIRT1

affects_activity of

gene/protein

NFKB1

Drugbank entries Show/Hide entries for NFKB1
Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61648

gene/protein

SIRT1

affects_activity of

gene/protein

PER2

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61649

gene/protein

SIRT1

affects_activity of

gene/protein

CRTC2

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61650

gene/protein

SIRT1

affects_activity of

gene/protein

E2F1

Comment Substrates / targets of Sirt1 are p53, PGC-1alpha, HIF1a and HIF2a, LXR (liver X receptor), SREB-Ps, FXR (farnesoid X receptor), NF-kappaB, PER2 (period circadian protein homolog 2), CRTC2 (CREB-regulated transcription coactivator 2), E2F1, and KU70.
Formal Description
Interaction-ID: 61651

gene/protein

SIRT1

affects_activity of

gene/protein

XRCC6

Comment Resveratrol cannot stimulate Sirt1 activity without a functional AMPK. It is proposed that Sirt1 is a downstream AMPK effector.
Formal Description
Interaction-ID: 61652

drug/chemical compound

Resveratrol

increases_activity of

gene/protein

SIRT1

depending on a functional AMPK.
Drugbank entries Show/Hide entries for Resveratrol
Comment Hydroxytyrosol, a molecule mainly derived from olives, increases Sirt1 expression.
Formal Description
Interaction-ID: 61653

drug/chemical compound

Hydroxytyrosol

increases_expression of

gene/protein

SIRT1

Comment Sirt1 interacts with and deacetylates FoxO transcription factors.
Formal Description
Interaction-ID: 61654

gene/protein

SIRT1

interacts (colocalizes) with

gene/protein

FOXO

Comment Sirt1 interacts with and deacetylates FoxO transcription factors.
Formal Description
Interaction-ID: 61655

gene/protein

SIRT1

decreases_acetylation of

gene/protein

FOXO

Comment Sirt1 may be involved in autophagy by deacetylating Atg5, Atg7, and Atg8.
Formal Description
Interaction-ID: 61656

gene/protein

SIRT1

decreases_acetylation of

gene/protein

ATG5

Comment Sirt1 may be involved in autophagy by deacetylating Atg5, Atg7, and Atg8.
Formal Description
Interaction-ID: 61657

gene/protein

SIRT1

decreases_acetylation of

gene/protein

ATG7

Comment Sirt1 may be involved in autophagy by deacetylating Atg5, Atg7, and Atg8.
Formal Description
Interaction-ID: 61658

gene/protein

SIRT1

decreases_acetylation of

gene/protein

GABARAPL

Comment It has been demonstrated that AMPK does not directly phosphorylate SIRT1, but the effect of this kinase on lipid oxidation is to modify the NAD+/NADH ratio, thus modulating SIRT1 deacetylase activity. Some evidence indicates that the expression of Nampt (Nicotinamide phosphoribosyl-transferase), which is involved in the synthesis of NAD+ by the NAD+ salvage pathway, is induced by AMPK.
Formal Description
Interaction-ID: 61674

complex/PPI

AMPK

affects_activity of

gene/protein

SIRT1

via modifying the NAD+/NADH ratio.
Comment LKB1, upstream of AMPK activation, is target of Sirt1, which may regulate its acetylation status, intracellular localization, and activity.
Formal Description
Interaction-ID: 61676

gene/protein

SIRT1

affects_activity of

gene/protein

STK11

Comment SIRT1 overexpression in neurons is associated with a reduction in mTOR protein levels and activity, thus providing a new SIRT1 negative modulation of mTOR signaling.
Formal Description
Interaction-ID: 61677

gene/protein

SIRT1

decreases_expression of

gene/protein

MTOR

if SIRT1 is overexpressed, concerning the mTOR protein level.
Drugbank entries Show/Hide entries for MTOR
Comment SIRT1 overexpression in neurons is associated with a reduction in mTOR protein levels and activity, thus providing a new SIRT1 negative modulation of mTOR signaling.
Formal Description
Interaction-ID: 61679

gene/protein

SIRT1

decreases_activity of

gene/protein

MTOR

if SIRT1 is overexpressed.
Drugbank entries Show/Hide entries for MTOR
Comment SIRT1 overexpression in neurons is associated with a reduction in mTOR protein levels and activity, thus providing a new SIRT1 negative modulation of mTOR signaling.
Formal Description
Interaction-ID: 61680

gene/protein

SIRT1

decreases_activity of

process

TOR signaling

if SIRT1 is overexpressed.