Mumberg D, Wick M, Bürger C, Haas K, Funk M, Müller R
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, Emil-Mannkopff-Strasse 2, D-35033 Marburg, Germany.
Nucleic Acids Res. 1997 Jun 1;25(11):2098-105. doi: 10.1093/nar/25.11.2098.
Cyclin E is the regulatory subunit of the cdc2-related protein kinase cdk2 and is a rate limiting factor for the entry into S phase. To date, cyclin E is the only cyclin for which alternative splicing has been described. We report here the isolation of a new splice variant of cyclin E, termed cyclin ET, which has an internal deletion of 45 amino acids compared with the full-length cyclin E protein. Even though cyclin ETcontains an intact cyclin box, it is unable to complement a triple cln mutant strain of Saccharomyces cerevisiae or to interfere with rescue by cyclin E, indicating that an intact cyclin box is functionally insufficient. The expression pattern of cyclin ET during cell cycle entry, progression and differentiation differs from that of cyclin E. Thus, ET expression precedes that of the other isoforms during the G0-->S progression; it shows a sharp peak in early G1 in cells released from a mitotic block and is strongly down-regulated in terminally differentiated myeloid cells. These observations point to different functions for cyclin ET and E and show for the first time that the alternative splicing of cyclin E is a regulated mechanism governed by the cell cycle and differentiation.
细胞周期蛋白E是与细胞分裂周期蛋白2相关的蛋白激酶cdk2的调节亚基，是进入S期的限速因子。迄今为止，细胞周期蛋白E是唯一一种已被描述存在可变剪接的细胞周期蛋白。我们在此报告一种新的细胞周期蛋白E剪接变体的分离，称为细胞周期蛋白ET，与全长细胞周期蛋白E蛋白相比，它有45个氨基酸的内部缺失。尽管细胞周期蛋白ET含有完整的细胞周期蛋白框，但它无法补充酿酒酵母的三重cln突变株，也不能干扰细胞周期蛋白E的拯救作用，这表明完整的细胞周期蛋白框在功能上是不足的。细胞周期蛋白ET在细胞周期进入、进程和分化过程中的表达模式与细胞周期蛋白E不同。因此，在从G0期向S期转变过程中，ET的表达先于其他异构体；在从有丝分裂阻滞中释放的细胞中，它在G1早期显示出一个尖锐的峰值，而在终末分化的髓样细胞中则强烈下调。这些观察结果表明细胞周期蛋白ET和E具有不同的功能，并首次表明细胞周期蛋白E的可变剪接是一种受细胞周期和分化调控的机制。
