REST
REST (RE1-silencing transcription factor) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Wilms tumour.
Overview
Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier.
Open Targets scores its association with cancer at 0.63 (direct and indirect evidence; datatypes literature 0.99, genetic association 0.70, somatic mutation 0.47, genetic literature 0.58). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Wilms' Tumour.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · REST (RE1-silencing transcription factor) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Wilms tumour.
- 1 · What it is
REST (RE1-silencing transcription factor) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Wilms tumour.
- 2 · What goes wrong in cancer
Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells.
- 3 · How drugs use it
No product in this corpus aims at REST yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:9966 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q13127 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000084093 (association with cancer (MONDO_0004992) 0.63; (GraphQL API, CC0)); IntOGen REST (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells. Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes. Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression. Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 3. Repressor activity may be inhibited by forming heterodimers with isoform 3, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes. Location: Nucleus; Cytoplasm (UniProt). Locus 4q12 (HGNC).
- Wilms tumour: IntOGen driver in 1 cohort (WT)
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: IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"REST" OR ABSTRACT:"REST" OR TITLE:"RE1 silencing transcription factor" OR ABSTRACT:"RE1 silencing transcription factor" OR TITLE:"RE1-silencing transcription factor" OR ABSTRACT:"RE1-silencing transcription factor" OR TITLE:"DFNA27" OR ABSTRACT:"DFNA27") 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 REST, not a curated reading list.
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