BACTERIAL FUNCTION INVOLVED IN CELL GROWTH CONTROL

参与细胞生长控制的细菌功能

• 批准号: 3774336
• 负责人: S GOTTESMAN
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3774336
• 关键词: DNA replication; RNA; adenosinetriphosphatase; bacterial genetics; cell cycle; cell growth regulation; endopeptidases; enzyme induction /repression; enzyme mechanism; enzyme substrate; gene expression; histones; molecular cloning; nucleic acid structure; phosphorylation; protein biosynthesis; protein degradation; regulatory gene; stress proteins; transcription factor

We have been studying the role that protein degradation plays in regulating gene expression and have continued with studies on the linkages between chromosome synthesis and partition of chromosomes during cell division. Turnover of the natural substrates of the Lon ATP-dependent protease, N and SulA, has been shown to be independent of the heat shock protein DnaJ, while the activity of another substrate of Lon, the capsular polysaccharide positive regulator RcsA, has been shown to be dependent on DnaJ activity under most circumstances. These results suggest that the heat shock proteins are not an essential component of Lon-dependent degradation of natural substrates in vivo. The temperature sensitivity of capsule synthesis appears to be due to misfolding of RcsA in vivo; similar misfolding may occur in the absence of DnaJ. Studies on the regulation of rcsA transcription have led to the identification of a small RNA, DsrA RNA. Increased amounts of DsrA RNA lead to increased transcription of rcsA, apparently because the DsrA RNA participates in opening a silenced rcsA promoter. The histone-like protein, HNS, is necessary for silencing. We have continued to investigate the in vivo function of the Clp energy- dependent protease. The specificity of this protease in vivo seems to be dictated by the ATPase subunit. We have found that ClpX, an alternate ATPase subunit, and ClpP mediate degradation of lambda O protein, as well as a number of other substrates. Another possible ATPase subunit has been found by sequence comparisons and its role in in vivo degradation is being examined. We have also been studying the regulatory events of the cell cycle using the mbr mutants, which have an alteration in DNA content per cell. We have been focusing on mbrA, which affects the coupling of DNA replication to cell elongation and have identified several genes required for mbrA to function. In addition, we have cloned mbrA and begun to analyze the physical structure of the gene. Further characterization of mbrA and its suppressors should elucidate the critical role it plays in cell cycle regulation.

我们一直在研究蛋白质降解在 调节基因表达，并继续研究两者之间的联系 细胞内染色体合成与染色体分裂之间的关系 组织。Lon-ATP依赖的天然底物的周转 蛋白水解酶N和Sula已被证明不受热休克的影响 蛋白质Dna J，而Lon的另一种底物--衣壳的活性 多糖正向调节因子RCSA，已被证明依赖于 DNAJ在大多数情况下都有活动。这些结果表明， 热休克蛋白不是Lon依赖的必要成分 天然底物的体内降解。的温度敏感性 胶囊合成似乎是由于RCSA在体内的错误折叠；类似 在没有DNAJ的情况下，可能会发生错误折叠。关于监管的若干问题研究 RCSA转录导致了一种小RNA DSRA的鉴定 核糖核酸。DSRA RNA数量的增加导致转录增加 RCSA，显然是因为DSRA RNA参与打开沉默的 RCSA启动子。组蛋白样蛋白HNS是沉默所必需的。 我们继续研究CLP能量的体内功能- 依赖的蛋白酶。这种蛋白水解酶在体内的特异性似乎是 由ATPase亚单位决定。我们发现了ClpX，一种替代 ATPase亚基和ClpP也介导了lambda O蛋白的降解 作为许多其他底物。另一个可能的ATPase亚基是 通过序列比较发现其在体内降解中的作用 检查过了。我们也一直在研究细胞的调节事件 使用MBR突变体进行循环，这些突变体在每个 手机。我们一直在关注mbrA，它影响DNA的偶联 复制到细胞伸长，并确定了几个所需的基因 MbrA才能发挥作用。此外，我们已经克隆了mbrA并开始 分析基因的物理结构。进一步的特征描述 MbrA及其抑制者应该阐明它在 细胞周期调节。