GSK-3 Promotes Conditional Association of CREB and Its Coactivators with MEIS1 to Facilitate HOX-Mediated Transcription and Oncogenesis
Copyright policy )GSK-3 Promotes Conditional Association of CREB and Its Coactivators with MEIS1 to Facilitate HOX-Mediated Transcription and Oncogenesis
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.
Cancer Research, Indoles, Down-Regulation, CELLCYCLE, Models, Biological, Maleimides, Glycogen Synthase Kinase 3, Mice, Cell Line, Tumor, Animals, Humans, CELL CYCLE, Cyclic AMP Response Element-Binding Protein, Myeloid Ecotropic Viral Integration Site 1 Protein, Cell Proliferation, Homeodomain Proteins, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Cell Biology, CREB-Binding Protein, DNA-Binding Proteins, Mice, Inbred C57BL, Leukemia, Myeloid, Acute, Cell Transformation, Neoplastic, Oncology
Cancer Research, Indoles, Down-Regulation, CELLCYCLE, Models, Biological, Maleimides, Glycogen Synthase Kinase 3, Mice, Cell Line, Tumor, Animals, Humans, CELL CYCLE, Cyclic AMP Response Element-Binding Protein, Myeloid Ecotropic Viral Integration Site 1 Protein, Cell Proliferation, Homeodomain Proteins, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Cell Biology, CREB-Binding Protein, DNA-Binding Proteins, Mice, Inbred C57BL, Leukemia, Myeloid, Acute, Cell Transformation, Neoplastic, Oncology
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).114 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!