Haugwitz Ulrike, Wasner Mark, Wiedmann Marcus, Spiesbach Katja, Rother Karen, Mössner Joachim, Engeland Kurt
Department of Internal Medicine II, University of Leipzig, Max Bürger Research Center, Johannisallee 30, D-04103 Leipzig, Germany.
Nucleic Acids Res. 2002 May 1;30(9):1967-76. doi: 10.1093/nar/30.9.1967.
The cdc25C phosphatase participates in regulating transition from the G2 phase of the cell cycle to mitosis by dephosphorylating cyclin-dependent kinase 1. The tumor suppressor p53 down-regulates expression of cdc25C as part of G2/M checkpoint control. Transcription of cdc25C oscillates during the cell cycle with no expression in resting cells and maximum transcription in G2. We had identified earlier a new mechanism of cell cycle-dependent transcription that is regulated by a cell cycle-dependent element (CDE) in conjunction with a cell cycle genes homology region (CHR). The human cdc25C gene was the first example. CDE/CHR tandem elements have since been found in promoters of many cell cycle genes. Here we show that the mouse cdc25C gene is regulated by a CHR but does not hold a CDE. Therefore, it is the first identified gene with CHR-dependent transcriptional regulation during the cell cycle not relying on a CDE located upstream of it. The CHR leads to repression of cdc25C transcription early in the cell cycle and directs a release of this repression in G2. Furthermore, we find that this CHR can cooperate in cell cycle-dependent transcription with elements placed directly upstream of it binding E2F, Sp1 or Sp3 transcription factors.
细胞分裂周期蛋白25C磷酸酶(cdc25C)通过使细胞周期蛋白依赖性激酶1去磷酸化,参与调控细胞周期从G2期向有丝分裂的转变。肿瘤抑制因子p53下调cdc25C的表达,作为G2/M期检查点控制的一部分。cdc25C的转录在细胞周期中呈振荡变化,静止细胞中无表达,在G2期转录达到最大值。我们之前已经确定了一种新的细胞周期依赖性转录机制,该机制由细胞周期依赖性元件(CDE)与细胞周期基因同源区域(CHR)共同调控。人类cdc25C基因是首个例子。此后,在许多细胞周期基因的启动子中都发现了CDE/CHR串联元件。在此我们表明,小鼠cdc25C基因受CHR调控,但不含有CDE。因此,它是首个被鉴定出的在细胞周期中依赖CHR进行转录调控且不依赖其上游CDE的基因。CHR在细胞周期早期导致cdc25C转录受到抑制,并在G2期解除这种抑制。此外,我们发现该CHR可与直接位于其上游的结合E2F、Sp1或Sp3转录因子的元件协同进行细胞周期依赖性转录。