Enhanced degradation of MDM2 by a nuclear envelope component, mouse germ cell-less.
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.
Mesh Terms:
Animals, Blotting, Northern, Blotting, Western, Cell Line, Cell Nucleus, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, Humans, Luciferases, Mice, Microscopy, Fluorescence, Nuclear Envelope, Nuclear Proteins, Plasmids, Precipitin Tests, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Two-Hybrid System Techniques, Ubiquitin
Animals, Blotting, Northern, Blotting, Western, Cell Line, Cell Nucleus, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, Humans, Luciferases, Mice, Microscopy, Fluorescence, Nuclear Envelope, Nuclear Proteins, Plasmids, Precipitin Tests, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Two-Hybrid System Techniques, Ubiquitin
Biochem. Biophys. Res. Commun.
Date: Sep. 05, 2003
PubMed ID: 12927808
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