Abstract
A mouse homologue of Drosophila germ cell less, mouse germ cell less-1 (mgcl-1), encodes a nuclear envelope component essential for nuclear integrity. To analyze the molecular function of mGCL-1, we carried out two hybrid screening and found that mGCL-1 bound to the gene product of tumor susceptibility gene 101 (tsg101). Effects of mGCL-1 on the expression of MDM2-p53 axis were examined, since TSG101 has been shown to elevate the amount of MDM2 by inhibiting the ubiquitination. mGCL-1 significantly reduced the amount of MDM2 probably by changing the sub-cellular localization of the MDM2 and facilitating the ubiquitination of MDM2. In addition, the amount of p53 was increased and transactivation by p53 was enhanced by mGCL-1. Thus, mGCL-1 turned out to be a factor modulating MDM2-p53 axis by enhanced degradation of MDM2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Northern
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Blotting, Western
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Cell Line
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Cell Nucleus / metabolism*
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DNA-Binding Proteins / metabolism
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Endosomal Sorting Complexes Required for Transport
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Humans
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Luciferases / metabolism
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Mice
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Microscopy, Fluorescence
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Nuclear Envelope / metabolism*
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Nuclear Proteins / metabolism*
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Nuclear Proteins / physiology*
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Plasmids / metabolism
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Precipitin Tests
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Protein Binding
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-mdm2
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Transcription Factors / metabolism
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Transcription, Genetic
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / metabolism
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Two-Hybrid System Techniques
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Ubiquitin / metabolism
Substances
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DNA-Binding Proteins
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Endosomal Sorting Complexes Required for Transport
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Gcl protein, mouse
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Nuclear Proteins
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Proto-Oncogene Proteins
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Transcription Factors
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Tsg101 protein
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Tumor Suppressor Protein p53
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Ubiquitin
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Luciferases
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MDM2 protein, human
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Mdm2 protein, mouse
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Proto-Oncogene Proteins c-mdm2