Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells (Publication with Expression of Concern. See vol. 295, pg. 8875, 2020) (Withdrawn Publication. See vol. 296, 2021) (Withdrawn Publication. See vol. 296, 2021)
Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells (Publication with Expression of Concern. See vol. 295, pg. 8875, 2020) (Withdrawn Publication. See vol. 296, 2021) (Withdrawn Publication. See vol. 296, 2021)
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DOI：
10.1074/jbc.m312895200
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发表时间：
2004-03-19
影响因子：
4.8
通讯作者：
Cao, XT
中科院分区：
文献类型：
--
作者：
Yang, LJ;Li, N;Cao, XT
我们报告的克隆和功能特性的人细胞周期蛋白L2，一个新的成员的细胞周期蛋白家族。人细胞周期蛋白L2与细胞周期蛋白L1、K、T1、T2和C具有显著的同源性，它们通过RNA聚合酶II的C-末端结构域的磷酸化参与转录调节。细胞周期蛋白L2蛋白含有N-末端“细胞周期蛋白盒”和C-末端重复的交替丝氨酸和丝氨酸的二肽，这是剪接因子SR家族的标志。本研究还克隆了人细胞周期蛋白L2的一种新的同种型和小鼠同源物。人细胞周期蛋白L2在正常人体组织和肿瘤细胞中广泛表达。我们在这里表明，细胞周期蛋白L2与剪接因子SC-35和9 G8共同定位在核斑点内，它与过度磷酸化，但不hypophosphorylated，RNA聚合酶II和CDK p110 PITSLRE激酶通过其N-末端细胞周期蛋白结构域。它还可以通过其RS重复区域与SC-35和9 G8结合。重组细胞周期蛋白L2蛋白在体外可刺激mRNA剪接。过表达cyclin L2可抑制人肝癌SMMC 7721细胞的生长，诱导细胞凋亡。该过程涉及p53和Bax的上调以及Bcl-2的表达降低。结果提示，cyclin L2是cyclin家族的一个新成员，它可能通过调控某些凋亡相关因子的转录和RNA加工，导致肿瘤细胞生长抑制和凋亡。
We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase II. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase II and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.