Human Gene Set: IGARASHI_ATF4_TARGETS_DN


Standard name IGARASHI_ATF4_TARGETS_DN
Systematic name M4779
Brief description Genes down-regulated in A549 cells (lung cancer) after knockdown of ATF4 [GeneID=468] by RNAi.
Full description or abstract The mechanisms underlying cellular drug resistance have been extensively studied, but little is known about its regulation. We have previously reported that activating transcription factor 4 (ATF4) is upregulated in cisplatin-resistant cells and plays a role in cisplatin resistance. Here, we find out a novel relationship between the circadian transcription factor Clock and drug resistance. Clock drives the periodical expression of many genes that regulate hormone release, cell division, sleep-awake cycle and tumor growth. We demonstrate that ATF4 is a direct target of Clock, and that Clock is overexpressed in cisplatin-resistant cells. Furthermore, Clock expression significantly correlates with cisplatin sensitivity, and that the downregulation of either Clock or ATF4 confers sensitivity of A549 cells to cisplatin and etoposide. Notably, ATF4-overexpressing cells show multidrug resistance and marked elevation of intracellular glutathione. The microarray study reveals that genes for glutathione metabolism are generally downregulated by the knockdown of ATF4 expression. These results suggest that the Clock and ATF4 transcription system might play an important role in multidrug resistance through glutathione-dependent redox system, and also indicate that physiological potentials of Clock-controlled redox system might be important to better understand the oxidative stress-associated disorders including cancer and systemic chronotherapy.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17297441   Authors: Igarashi T,Izumi H,Uchiumi T,Nishio K,Arao T,Tanabe M,Uramoto H,Sugio K,Yasumoto K,Sasaguri Y,Wang KY,Otsuji Y,Kohno K
Exact source Suppl. info: fold change < 1
Related gene sets (show 1 additional gene sets from the source publication)

(show 10 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform or
identifier namespace
AFFY_HG_U133
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 98 genes
Gene families ? Categorize these 98 genes by gene family
Show members (show 121 source identifiers mapped to 98 genes)
Version history 3.0: First introduced

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