SIRT1
SIRT1 (NAD-dependent protein deacetylase sirtuin-1) is a protein that switches other genes on and off. The public catalogues list it as a drug target and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Pancreatic ductal adenocarcinoma.
Overview
NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively.
CIViC holds 2 clinical evidence items and 0 assertions across 1 variant, naming Niacinamide.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · SIRT1 (NAD-dependent protein deacetylase sirtuin-1) is a protein that switches other genes on and off. The public catalogues list it as a drug target and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Pancreatic ductal adenocarcinoma.
- 1 · What it is
SIRT1 (NAD-dependent protein deacetylase sirtuin-1) is a protein that switches other genes on and off. The public catalogues list it as a drug target and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Pancreatic ductal adenocarcinoma.
- 2 · What goes wrong in cancer
NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy.
- 3 · How drugs use it
No product in this corpus aims at SIRT1 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:14929 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q96EB6 (protein name, function text, keywords and locations (REST API)); CIViC gene SIRT1 (2 evidence items, 0 assertions, 1 variants; diseases: Pancreatic Ductal Carcinoma, Pancreatic Cancer (GraphQL API, CC0))
Biology
NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. Location: Nucleus, PML body; Cytoplasm; Nucleus; Nucleus, nucleoplasm (UniProt). Locus 10q21.3 (HGNC).
- Pancreatic ductal adenocarcinoma: CIViC evidence names this disease
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 1 therapies; CIViC holds 2 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Pancreatic Ductal Carcinoma.
Latest papers
topQuery for this target: (TITLE:"SIRT1" OR ABSTRACT:"SIRT1" OR TITLE:"sirtuin 1" OR ABSTRACT:"sirtuin 1" OR TITLE:"NAD-dependent protein deacetylase sirtuin-1" OR ABSTRACT:"NAD-dependent protein deacetylase sirtuin-1" OR TITLE:"SIR2L1" OR ABSTRACT:"SIR2L1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about SIRT1, not a curated reading list.