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Menin critically links MLL proteins with LEDGF on cancer-associated target genes.

Cancer cell | Jul 8, 2008

Menin displays the unique ability to either promote oncogenic function in the hematopoietic lineage or suppress tumorigenesis in the endocrine lineage; however, its molecular mechanism of action has not been defined. We demonstrate here that these discordant functions are unified by menin's ability to serve as a molecular adaptor that physically links the MLL (mixed-lineage leukemia) histone methyltransferase with LEDGF (lens epithelium-derived growth factor), a chromatin-associated protein previously implicated in leukemia, autoimmunity, and HIV-1 pathogenesis. LEDGF is required for both MLL-dependent transcription and leukemic transformation. Conversely, a subset of menin mutations in multiple endocrine neoplasia type 1 patients abrogate interaction with LEDGF while preserving MLL interaction but nevertheless compromise MLL/menin-dependent functions. Thus, LEDGF critically associates with MLL and menin at the nexus of transcriptional pathways that are recurrently targeted in diverse diseases.

Pubmed ID: 18598942 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Animals | Cell Transformation, Neoplastic | Chromatin | Chromatin Assembly and Disassembly | Gene Expression Regulation, Leukemic | HeLa Cells | Histone-Lysine N-Methyltransferase | Homeodomain Proteins | Humans | Leukemia | Mice | Mice, Inbred C57BL | Multiple Endocrine Neoplasia Type 1 | Mutation | Myeloid Progenitor Cells | Myeloid-Lymphoid Leukemia Protein | Protein Binding | Protein Methyltransferases | Protein Structure, Tertiary | Proto-Oncogene Proteins | RNA Interference | Time Factors | Transcription Factors | Transcription, Genetic | Transduction, Genetic | Tumor Suppressor Proteins | U937 Cells

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Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA116606
  • Agency: NCI NIH HHS, Id: R01 CA116606-04
  • Agency: NCI NIH HHS, Id: CA55029
  • Agency: NCI NIH HHS, Id: R01 CA055029
  • Agency: NCI NIH HHS, Id: R01 CA055029-18
  • Agency: NCI NIH HHS, Id: CA116606

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