Abstract
To elucidate the contribution of the N-Myc protein to neuroblastomas we have used a synthetic inducible expression system on the basis of the tetracycline repressor of E coli to reversibly express N-myc in a human neuroblastoma cell line in which expression of endogenous N-myc is barely detectable. Like the c-Myc protein, N-Myc up-regulates the expression of both alpha-prothymosin and ornithine decarboxylase. Induction of N-myc increases both the rate of DNA-synthesis and the proliferation rate, and shortens the G1 phase of the cell cycle. A comparison of cell populations in which the presence of N-Myc protein was restricted to different parts of G(zero)/G1 revealed that N-Myc is rate-limiting for cell cycle progression during the first 5 h after serum stimulation of quiescent cells providing direct evidence that Myc-proteins act early after mitogenic stimulation of quiescent cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic-Leucine Zipper Transcription Factors
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Biopolymers
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Cell Nucleus / metabolism
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DNA-Binding Proteins / metabolism
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G1 Phase
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Gene Expression Regulation, Enzymologic
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Gene Expression Regulation, Neoplastic
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Humans
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Mitogens / pharmacology*
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Neuroblastoma / genetics*
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Neuroblastoma / pathology
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Ornithine Decarboxylase / genetics*
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Protein Precursors / genetics*
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Proto-Oncogene Proteins c-myc / genetics*
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Proto-Oncogene Proteins c-myc / metabolism
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Resting Phase, Cell Cycle
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S Phase*
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Thymosin / analogs & derivatives*
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Thymosin / genetics
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Transcription Factors*
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Tumor Cells, Cultured
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic-Leucine Zipper Transcription Factors
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Biopolymers
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DNA-Binding Proteins
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MAX protein, human
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Mitogens
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Myc associated factor X
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Protein Precursors
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Proto-Oncogene Proteins c-myc
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Transcription Factors
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prothymosin alpha
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Thymosin
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Ornithine Decarboxylase