Abstract
MCT-1 is an oncogene that was initially identified in a human T cell lymphoma and has been shown to induce cell proliferation as well as activate survival-related pathways. MCT-1 contains the PUA domain, a recently described RNA-binding domain that is found in several tRNA and rRNA modification enzymes. Here, we established that MCT-1 protein interacts with the cap complex through its PUA domain and recruits the density-regulated protein (DENR/DRP), containing the SUI1 translation initiation domain. Through the use of microarray analysis on polysome-associated mRNAs, we showed that up-regulation of MCT-1 was able to modulate the translation profiles of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs, despite equivalent levels of mRNAs in the cytoplasm. Our data establish a role for MCT-1 in translational regulation, and support a linkage between translational control and oncogenesis.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Cycle Proteins / biosynthesis
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Cell Cycle Proteins / genetics*
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Cell Cycle Proteins / metabolism*
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Cell Transformation, Neoplastic / genetics
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Eukaryotic Initiation Factors / genetics
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Eukaryotic Initiation Factors / metabolism
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Gene Expression Regulation, Neoplastic / genetics
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HeLa Cells
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Humans
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Mice
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NIH 3T3 Cells
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Oncogene Proteins / biosynthesis
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Oncogene Proteins / genetics*
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Oncogene Proteins / metabolism*
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Protein Biosynthesis / physiology*
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Protein Structure, Tertiary
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RNA Caps / genetics*
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RNA Caps / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Up-Regulation
Substances
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Cell Cycle Proteins
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DENR protein, human
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EIF1 protein, human
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Eukaryotic Initiation Factors
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MCTS1 protein, human
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Neoplasm Proteins
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Nerve Tissue Proteins
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Oncogene Proteins
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RNA Caps