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PMID:12927808

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Citation

Masuhara, M, Nagao, K, Nishikawa, M, Kimura, T and Nakano, T (2003) Enhanced degradation of MDM2 by a nuclear envelope component, mouse germ cell-less. Biochem. Biophys. Res. Commun. 308:927-32

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.

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Keywords

Animals; Blotting, Northern; Blotting, Western; Cell Line; Cell Nucleus/metabolism; DNA-Binding Proteins/metabolism; Endosomal Sorting Complexes Required for Transport; Humans; Luciferases/metabolism; Mice; Microscopy, Fluorescence; Nuclear Envelope/metabolism; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; Plasmids/metabolism; Precipitin Tests; Protein Binding; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-mdm2; Transcription Factors/metabolism; Transcription, Genetic; Transcriptional Activation; Transfection; Tumor Cells, Cultured; Tumor Suppressor Protein p53/metabolism; Two-Hybrid System Techniques; Ubiquitin/metabolism

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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