Human Gene Set: PEART_HDAC_PROLIFERATION_CLUSTER_DN


Standard name PEART_HDAC_PROLIFERATION_CLUSTER_DN
Systematic name M1421
Brief description Cell proliferation genes down-regulated by histone deacetylase (HDAC) inhibitors SAHA and depsipeptide [PubChem=5311;5352062].
Full description or abstract Histone deacetylase inhibitors (HDACis) inhibit tumor cell growth and survival, possibly through their ability to regulate the expression of specific proliferative and/or apoptotic genes. However, the HDACi-regulated genes necessary and/or sufficient for their biological effects remain undefined. We demonstrate that the HDACis suberoylanilide hydroxamic acid (SAHA) and depsipeptide regulate a highly overlapping gene set with at least 22% of genes showing altered expression over a 16-h culture period. SAHA and depsipeptide coordinately regulated the expression of several genes within distinct apoptosis and cell cycle pathways. Multiple genes within the Myc, type beta TGF, cyclin/cyclin-dependent kinase, TNF, Bcl-2, and caspase pathways were regulated in a manner that favored induction of apoptosis and decreased cellular proliferation. APAF-1, a gene central to the intrinsic apoptotic pathway, was induced by SAHA and depsipeptide and shown to be important, but not essential, for HDACi-induced cell death. Overexpression of p16(INK4A) and arrest of cells in G(1) can suppress HDACi-mediated apoptosis. Although p16(INK4A) did not affect the genome-wide transcription changes mediated by SAHA, a small number of apoptotic genes, including BCLXL and B-MYB, were differentially regulated in a manner consistent with attenuated HDACi-mediated apoptosis in arrested cells. We demonstrate that different HDACi alter transcription of a large and common set of genes that control diverse molecular pathways important for cell survival and proliferation. The ability of HDACi to target multiple apoptotic and cell proliferation pathways may provide a competitive advantage over other chemotherapeutic agents because suppression/loss of a single pathway may not confer resistance to these agents.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15738394   Authors: Peart MJ,Smyth GK,van Laar RK,Bowtell DD,Richon VM,Marks PA,Holloway AJ,Johnstone RW
Exact source Table 3S: down-regulated genes
Related gene sets (show 1 additional gene sets from the source publication)

(show 15 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Kate Stafford (MSigDB Team)
Source platform or
identifier namespace
HUMAN_SEQ_ACCESSION
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 71 genes
Gene families ? Categorize these 71 genes by gene family
Show members (show 83 source identifiers mapped to 71 genes)
Version history 3.1: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.