Wang Z, Iwasaki M, Ficara F, Lin C, Matheny C, Wong SH et al.. GSK-3 promotes conditional association of CREB and its coactivators with MEIS1 to facilitate HOX-mediated transcription and oncogenesis. Cancer Cell 17: 597-608

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cancer cell (Impact Factor: 23.52). 06/2010; 17(6):597-608. DOI: 10.1016/j.ccr.2010.04.024
Source: PubMed


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.

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Available from: Francesca Ficara, Mar 13, 2014
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