Abstract
The LYL1 gene was first identified upon the molecular characterization of the t(7;9)(q35;p13) translocation associated with some human T-cell acute leukemias (T-ALLs). In adult tissues, LYL1 expression is restricted to hematopoietic cells with the notable exclusion of the T cell lineage. LYL1 encodes a basic helix-loop-helix (bHLH) protein highly related to TAL-1, whose activation is also associated with a high proportion of human T-ALLs. A yeast two-hybrid system was used to identify proteins that specifically interact with LYL1 and might mediate its activities. We found that p105, the precursor of NF-kappaB1 p50, was the major LYL1-interacting protein in this system. The association between LYL1 and p105 was confirmed both in vitro and in vivo in mammalian cells. Biochemical studies indicated that the interaction was mediated by the bHLH motif of LYL1 and the ankyrin-like motifs of p105. Ectopic expression of LYL1 in a human T cell line caused a significant decrease in NF-kappaB-dependent transcription, associated with a reduced level of NF-kappaB1 proteins.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Basic Helix-Loop-Helix Transcription Factors
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Cell Line
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DNA, Complementary / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Glutathione Transferase / metabolism
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Helix-Loop-Helix Motifs*
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Humans
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I-kappa B Proteins*
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Jurkat Cells
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K562 Cells
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Leukemia-Lymphoma, Adult T-Cell / metabolism
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NF-KappaB Inhibitor alpha
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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NF-kappa B p50 Subunit
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Protein Precursors / genetics
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Protein Precursors / metabolism*
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Proto-Oncogene Proteins*
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T-Cell Acute Lymphocytic Leukemia Protein 1
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Transcription Factors*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA, Complementary
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DNA-Binding Proteins
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I-kappa B Proteins
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LYL1 protein, human
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NF-kappa B
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NF-kappa B p50 Subunit
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NFKBIA protein, human
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Neoplasm Proteins
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Protein Precursors
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Proto-Oncogene Proteins
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T-Cell Acute Lymphocytic Leukemia Protein 1
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Transcription Factors
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TAL1 protein, human
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NF-KappaB Inhibitor alpha
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Glutathione Transferase