Transcriptional elongation factor and its implication in human disease

转录延伸因子及其在人类疾病中的意义

基本信息

批准号：
13470507
负责人：
KITAJIMA Shigetaka
金额：
$ 9.34万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470507/
关键词：
Transcriptional elongation Elongin Elongin A knock-out Growth arrest Hypemuclear cells Elongin Agene family Elongin A3 Activation by BC 転写制御転写伸長因子伸長因子活性制御伸長因子ノックアウト増殖障害伸長因子病 ELLホモログ ES細胞増殖低下

项目摘要

Transcriptional elongation is one of the major regulatory steps in gene expression by RNA polymerase II. Elongin is a general elongation factor which may be involved in oncogenesis associated with von Hippel Lindau (VHL) disease. To clarify the molecular basis of biological function of elongjn, we performed gene targeting of elongin A, and also cloned a novel elongin A gene family member, elongin A3.(1) Both alleles of Elongin A gene were disrupted in mouse embryonic stem (ES) cells. The cells showed significant growth defect, and had a higher number of cells at G2/M phase of cell cycle. Furthermore, elongin A deficient cells showed DNA content over 8n. Both microarray cDNA analysis and RNA protection assay showed that only a subset of genes, at least 2〜3 %, including those of cell cycle-related genes, were affected in elongin A-deficient cells. The data suggested that elongin A is not essential for genreral gene transcription, but is required for proper progression of cell cycle.(2) A novel elongin A gene family, elongin A3, was identified. Elongin A3 was composed of 553 amino acids with SII homology and elongin BC binding sequence. Recombinant A3 protein was active in transcriptional elongation, and bind elongin BC. A biochemical assay suggested that elongin A and A3 might function in not a complementary but competitive way. Thus, elongin A gene family interacts each other to modulate activity of the another member.

转录延伸是 RNA 聚合酶 II 基因表达的主要调控步骤之一。 Elongin 是一种通用延伸因子，可能参与与 von Hippel Lindau (VHL) 疾病相关的肿瘤发生。我们对elongin A进行了基因打靶，并克隆了一个新的elongin A基因家族成员，elongin A3。（1）小鼠中Elongin A基因的两个等位基因均被破坏胚胎干（ES）细胞显示出明显的生长缺陷，并且在细胞周期的G2/M期具有较高数量的细胞，此外，elongin A缺陷的细胞显示DNA含量超过8n。研究表明，在 elongin A 缺陷细胞中，只有一部分基因（至少 2-3%）受到影响，这些数据表明 elongin A 对于流派基因转录不是必需的，但却是必需的。 (2)鉴定出一个新的elongin A基因家族elongin A3，由553个氨基酸组成，具有SII同源性，重组elongin A3蛋白在转录延伸中具有活性。结合 elongin BC。生化分析表明 elongin A 和 A3 可能以非互补而是竞争的方式发挥作用，因此，elongin A 基因家族相互作用以调节 BC 的活性。另一位成员。