CHARACTERIZATION OF THE CELL CYCLE REGULATED GENE HG1.1

描述（改编自申请人摘要）：监管机构 控制进入和退出细胞周期的机制似乎是 重要的发展肿瘤，因为这种异常表明 明显缺乏适当的细胞生长控制。 这可能是 由于缺乏控制，调节退出细胞周期，通过 肿瘤抑制基因的作用，或通过肿瘤抑制基因进入细胞周期， 显性致癌基因的作用。 一种当前的细胞周期模型 调节认为G1期代表了细胞 要么在退出细胞周期之前停止增殖， 分化，变得静止或变得致力于继续通过 另一个细胞周期。 虽然有些成分被认为是调节这一点的 已经鉴定了许多系统（例如p34 cdc 2、RB 105、G1期细胞周期蛋白）， 细节仍然是个谜。 最近，一种独特的人类G1期特异性 cDNA（hG1.1）是从一个低等植物的消减cDNA文库中分离得到的， 丰富的G1期转录本。 该基因的转录发生在 在连续细胞的G1期期间， 循环和从静止状态返回。 因此，该cDNA可能代表了一种 一种新的细胞周期调节剂，可能作为G1期的一部分参与 gateway. 拟议研究的总体目标是阐明 调节细胞如何决定其在G1期的反应的机制， 表征这种G1期特异性转录物的作用， 将其功能与其他已知的G1期调节因子的功能相关联 基因. 这项研究的目的是扩大克隆 并进一步表征hG1.1的生物学作用。 克隆 所用策略选择用于G1期特异性表达;然而， 需要进一步的表征来确定hG1.1在 调节细胞周期进程。 具体目标将 确定hG1.1过表达和低表达对正常细胞的影响 周期进展以及这种效应是否特定于特定的细胞周期 相位 具体目标是：（1）全长克隆和测序 cDNA编码G1期特异性mRNA hG1.1，一种人细胞周期时相- 特异性转录物，（2）表征未调节的 hG1.1过表达对细胞周期进程的影响 转染测定，和（3）表征抑制的影响， hG1.1表达对细胞周期进程的影响 寡核苷酸补料。

DESCRIPTION (Adapted from the applicant's abstract): The regulatory mechanisms controlling entry and exit from the cell cycle appear to be important in development of neoplasia because this abnormality indicates an apparent lack of appropriate cell growth control. This may be the result of a lack of control in regulating exit from the cell cycle, through the action of tumor suppressor genes, or entry into the cell cycle through the action of the dominant oncogenes. One current model of cell cycle regulation holds that G1 phase represents a gateway during which cells either cease to proliferate before retiring from the cell cycle to differentiate, become quiescent or become committed to proceed through another cell cycle. While some of the components thought to regulate this system have been identified (eg.p34cdc2, RB105, G1 phase cyclins) many of the details remain enigmatic. Recently, a unique human G1 phase-specific cDNA (hG1.1) has been isolated from a subtractive cDNA library of lower abundance G1 phase transcripts. Transcription of this gene occurs during a very narrow window of time during G1 phase of both the continuous cell cycle and re-entry from quiescence. Therefore, this cDNA may represent a novel cell cycle regulator and may participate as part of the G1 phase gateway. The overall goal of the proposed research is to elucidate part of the mechanism regulating how a cell determines its response in G1 phase by characterizing the role of this G1 phase-specific transcript and correlating its function with those of other known G1 phase regulatory genes. The objectives of this research are designed to extend the cloning and further characterize the biological role of hG1.1. The cloning strategy employed selected for G1 phase-specific expression; however, further characterization is required to determine the role hG1.1 plays in the regulation of cell cycle progression. The specific objectives will determine what effect over and underexpression of hG1.1 have on normal cell cycle progression and if this effect is specific to a particular cell cycle phase. The specific objectives are: (1) Clone and sequence full length cDNA encoding the G1 phase-specific mRNA hG1.1, a human cell cycle phase- specific transcript, (2) Characterize the effects of unregulated overexpression of hG1.1 on cell cycle progression in transient and stable transfection assays, and (3) Characterize the effects of inhibition of hG1.1 expression on cell cycle progression by the use of antisense oligonucleotide feeding.