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      GSK-3 Promotes Conditional Association of CREB and Its Coactivators with MEIS1 to Facilitate HOX-Mediated Transcription and Oncogenesis

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          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. Copyright 2010 Elsevier Inc. All rights reserved.

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          Author and article information

          Journal
          Cancer Cell
          Cancer Cell
          Elsevier BV
          15356108
          June 2010
          June 2010
          : 17
          : 6
          : 597-608
          Article
          10.1016/j.ccr.2010.04.024
          2919232
          20541704
          © 2010

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