Pines J, Hunter T
Wellcome/CRC Institute, Cambridge, UK.
EMBO J. 1994 Aug 15;13(16):3772-81. doi: 10.1002/j.1460-2075.1994.tb06688.x.
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.
我们之前已经表明，人类细胞周期蛋白A和B1在间期细胞中的定位存在差异；细胞周期蛋白A位于细胞核内，而细胞周期蛋白B1是一种细胞质蛋白。为了理解这种差异的基础，我们构建了缺失突变体以及这两种细胞周期蛋白之间的各种嵌合体，并通过瞬时转染在组织培养细胞中表达它们。我们发现，细胞周期蛋白B1的N端包含一个42个氨基酸的区域，该区域足以将通常位于细胞核的细胞周期蛋白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域会导致该蛋白进入细胞核。虽然细胞质保留信号区域在细胞周期蛋白框之外，但其序列在人类细胞周期蛋白B2中高度保守，并且对于将细胞周期蛋白B2保留在细胞质中既必要又充分。因此，我们提出B型细胞周期蛋白的亚细胞分布主要由N端的一个小区域决定，该区域将细胞周期蛋白-CDK复合物靶向细胞质中的特定结构。
