THE DIFFERENTIAL LOCALIZATION OF HUMAN CYCLIN-A AND CYCLIN-B IS DUE TO A CYTOPLASMIC RETENTION SIGNAL IN CYCLIN-B
THE DIFFERENTIAL LOCALIZATION OF HUMAN CYCLIN-A AND CYCLIN-B IS DUE TO A CYTOPLASMIC RETENTION SIGNAL IN CYCLIN-B
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DOI：
10.1002/j.1460-2075.1994.tb06688.x
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发表时间：
1994-08-15
期刊：
影响因子：
11.4
通讯作者：
HUNTER, T
中科院分区：
文献类型：
--
作者：
PINES, J;HUNTER, T
我们以前已经证明，在间期，人类细胞周期蛋白A和B1在细胞内的定位是不同的；细胞周期蛋白A是核的，细胞周期蛋白B1是细胞质蛋白。为了了解这种差异的基础，我们创建了两种细胞周期蛋白之间的缺失突变体和各种嵌合体，并通过瞬时转染在组织培养细胞中表达它们。我们发现Cyclin B1的N端含有一个42个氨基酸的区域，足以将正常的细胞核Cyclin A保留在细胞质中。相反，从细胞周期蛋白B1中删除细胞质保留信号区会导致蛋白质变成核。虽然细胞质保留信号区位于细胞周期蛋白盒外，但其序列在人细胞周期蛋白B2中非常保守，是保持细胞周期蛋白B2在细胞质中的必要条件和充分条件。因此，我们认为B型细胞周期蛋白的亚细胞分布主要是由N端的一小部分决定的，该区域将细胞周期蛋白-CDK复合体定位于细胞质中的特定结构。
We have shown previously that human cyclins A and B1 are localized differentially in the cell during interphase; cyclin A is nuclear and cyclin B1 is a cytoplasmic protein. To understand the basis of this difference we created deletion mutants and various chimeras between the two types of cyclin and expressed them in tissue culture cells by transient transfection. We find that the N-terminus of cyclin B1 contains a 42 amino acid region that is sufficient to retain the normally nuclear cyclin A in the cytoplasm. Conversely, deleting the cytoplasmic retention signal region from cyclin B1 causes the protein to become nuclear. Although the cytoplasmic retention signal region is outside the cyclin box, its sequence is well conserved in human cyclin B2, and is both necessary and sufficient to keep cyclin B2 in the cytoplasm. Thus we propose that the subcellular distribution of the B-type cyclins is determined primarily by a small region of the N-terminus which targets the cyclin-CDK complexes to particular structures in the cytoplasm.