Functional domains of necdin for protein–protein interaction, nuclear matrix targeting, and cell growth suppression
Functional domains of necdin for protein–protein interaction, nuclear matrix targeting, and cell growth suppression
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DOI：
10.1002/jcb.20345
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发表时间：
2005-03
影响因子：
4
通讯作者：
H. Taniura;M. Kobayashi;K. Yoshikawa
中科院分区：
文献类型：
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作者：
H. Taniura;M. Kobayashi;K. Yoshikawa
Necdin是一种主要在有丝分裂后神经元中表达的生长抑制因子。necdin基因参与基因组印迹相关神经发育障碍Prader-Willi综合征的病因学，属于法师基因家族。所有的法师家族蛋白都含有一个大的同源结构域，称为法师同源结构域（MHD）。在这里，我们的特点necdin的蛋白质-蛋白质相互作用，核基质靶向，细胞生长抑制所需的区域。包括necdin的整个MHD（氨基酸116-280）的区域是其与p53相互作用所必需的，而MHD内的氨基酸144-184和191-222区域是骨肉瘤SAOS-2细胞的核基质靶向和细胞生长抑制所必需的。氨基末端富含脯氨酸的酸性区域（氨基酸60-100）也是细胞生长抑制所必需的。四环素可调控的necdin过表达以可逆的方式诱导SAOS-2细胞的生长停滞，并且necdin过表达细胞显示出具有双核的大的扁平形态。与此相反，necdin突变体缺乏氨基酸191-222没有引起这样的变化。这些发现表明necdin的不同功能是通过其不同的结构域介导的。© 2004 Wiley利斯公司
Necdin is a growth suppressor expressed predominantly in postmitotic neurons. The necdin gene is involved in the etiology of the genomic imprinting‐associated neurodevelopmental disorder Prader–Willi syndrome and belongs to the MAGE gene family. All the MAGE family proteins contain a large homology domain termed the MAGE homology domain (MHD). We here characterize the regions of necdin required for the protein–protein interaction, nuclear matrix targeting, and cell growth suppression. The region including entire MHD (amino acids 116–280) of necdin was required for its interaction with p53, while the regions amino acids 144–184 and 191–222 within the MHD were required for both the nuclear matrix targeting and the cell growth suppression of osteosarcoma SAOS‐2 cells. The amino‐terminal proline‐rich acidic region (amino acids 60–100) was also necessary for cell growth suppression. Tetracycline‐regulatable overexpression of necdin induced growth arrest of SAOS‐2 cells in a reversible manner, and the necdin‐overexpressing cells showed a large, flattened morphology with double nuclei. In contrast, a necdin mutant lacking amino acids 191–222 did not induce such changes. These findings suggest that different functions of necdin are mediated via its distinct domains. © 2004 Wiley‐Liss, Inc.