一种核膜成分——小鼠无生殖细胞蛋白对MDM2的降解作用增强。
Enhanced degradation of MDM2 by a nuclear envelope component, mouse germ cell-less.
作者信息
Masuhara Masaaki, Nagao Kenji, Nishikawa Mitsuo, Kimura Tohru, Nakano Toru
机构信息
Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
出版信息
Biochem Biophys Res Commun. 2003 Sep 5;308(4):927-32. doi: 10.1016/s0006-291x(03)01497-9.
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.
果蝇生殖细胞缺失基因的小鼠同源物，即小鼠生殖细胞缺失基因-1（mgcl-1），编码一种对核完整性至关重要的核膜成分。为了分析mGCL-1的分子功能，我们进行了双杂交筛选，发现mGCL-1与肿瘤易感基因101（tsg101）的基因产物结合。由于TSG101已被证明可通过抑制泛素化来提高MDM2的量，因此我们检测了mGCL-1对MDM2-p53轴表达的影响。mGCL-1可能通过改变MDM2的亚细胞定位并促进MDM2的泛素化，显著降低了MDM2的量。此外，mGCL-1增加了p53的量，并增强了p53的反式激活作用。因此，mGCL-1被证明是一个通过增强MDM2降解来调节MDM2-p53轴的因子。
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