Human Gene Set: WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_DN


Standard name WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_DN
Systematic name M2132
Brief description Genes down-regulated in RS4;11 cells (MLL, mixed lineage leukemia) in response to SB216763 [PubChem=176158], an inhibitor of GSK3B [GeneID=2932].
Full description or abstract Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 20541704   Authors: Wang Z,Iwasaki M,Ficara F,Lin C,Matheny C,Wong SH,Smith KS,Cleary ML
Exact source Table 2S: Downregulated genes
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 3.1: First introduced

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