Abstract
Human T cell prolymphocytic leukemia can result from chromosomal translocations involving 14q32.1 or Xq28 regions. The regions encode a family of protooncogenes (TCL1, MTCP1, and TCL1b) of unknown function. In yeast two-hybrid screening, we found that TCL1 interacts with Akt. All TCL1 isoforms bind to the Akt pleckstrin homology domain. Both in vitro and in vivo TCL1 increases Akt kinase activity and as a consequence enhances substrate phosphorylation. In vivo, TCL1 stabilizes the mitochondrial transmembrane potential and enhances cell proliferation and survival. In vivo, TCL1 forms trimers, which associate with Akt. TCL1 facilitates the oligomerization and activation of Akt. Our data show that TCL1 is a novel Akt kinase coactivator, which promotes Akt-induced cell survival and proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / metabolism
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Cell Death
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Cell Division
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Cell Line
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Chromosomes, Human, Pair 14
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Cloning, Molecular
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Glycogen Synthase Kinase 3
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Humans
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Intracellular Membranes / physiology
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Lymphocyte Activation
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Membrane Potentials
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Mitochondria / physiology
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Proto-Oncogenes
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Recombinant Proteins / metabolism
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Spodoptera
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T-Lymphocytes / immunology
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Transfection
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Translocation, Genetic
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Tumor Cells, Cultured
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X Chromosome
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bcl-Associated Death Protein
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src Homology Domains
Substances
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BAD protein, human
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Carrier Proteins
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Proto-Oncogene Proteins
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Recombinant Proteins
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TCL1A protein, human
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bcl-Associated Death Protein
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3