Abstract
Notch1 intracellular domain (NICD) is the transcription factor which controls cell fate and differentiation in embryonic and tumor cells. Snail has a critical role which increases invasion and metastasis of cancer cell as a transcription factor and epigenetic regulator. Recently, we discovered NICD induced Snail degradation by direct binding interaction with Snail. In this experiment, we found that Snail suppressed transcriptional activity of the protein complex formed with NICD and RBPJk in nucleus. Moreover, Snail decreased transcription of NICD target genes via competing with MAML1, co-activator, in NICD complex. In conclusion, Snail inhibited NICD-mediated transcriptional activation of target genes by physical interaction with NICD.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding, Competitive
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Cell Line
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Humans
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Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics
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Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / metabolism
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Protein Structure, Tertiary
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Receptor, Notch1 / antagonists & inhibitors*
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Receptor, Notch1 / chemistry
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Receptor, Notch1 / genetics
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Receptor, Notch1 / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Snail Family Transcription Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation
Substances
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DNA-Binding Proteins
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
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MAML1 protein, human
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Multiprotein Complexes
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NOTCH1 protein, human
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RBPJ protein, human
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Receptor, Notch1
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Recombinant Proteins
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Snail Family Transcription Factors
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Transcription Factors