Analysis of a novel gene RA3, expression of which is upregulated during cell proliferation

分析新基因 RA3，其表达在细胞增殖过程中上调

• 批准号: 08670238
• 负责人: SHIRASAWA Hiroshi
• 金额: $ 1.34万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670238/
• 关键词: HPV; E6; cell proliferation

Cellular genes affected by human papillomavirus type 16 (HPV16) E6 protein were cloned by a differential hybridization technique. Two thirds of the cDNA clones were those that regulated during the cell cycle, such as HMG-IY (high mobility group protein-I[Y]), prothymosin-alpha, or ornithine decarboxylase. An unknown cDNA clone, RA3 was expressed during cell proliferation, and the expression was repressed by cell contact inhibition. Furthermore, repression of the RA3 expression was relieved by the expression of HPV16 E6.The RA3 cDNA was 1.3kb in length, and have no homology to other known genes. No known motif was also found in this new gene.The expression of the RA3 gene was correlated with the expression of the prothymosin-alpha and JUN.The expression of the prothymosin-alpha was activated by the HPV16E6 through the E2F motif of the c-myc gene. It was revealed that heterodimer complex of JUN and ATF2 is induced by the HPV16E6, followed by activation of genes that has CRE motif.Taken together, the RA3 gene appears to be regulated by the c-myc or JUN/ATF2 and involved in the mechanisms of the cell proliferation.

采用差分杂交技术克隆了人乳头瘤病毒16型（HPV16） E6蛋白感染的细胞基因。三分之二的cDNA克隆是那些在细胞周期中受到调节的，如HMG-IY（高迁移率组蛋白- i [Y]）、原胸腺肽- α或鸟氨酸脱羧酶。一个未知的cDNA克隆RA3在细胞增殖过程中表达，并通过细胞接触抑制抑制其表达。此外，hpv16e6的表达减轻了RA3表达的抑制。RA3 cDNA全长1.3kb，与其他已知基因无同源性。在这个新基因中也没有发现已知的基序。RA3基因的表达与原胸腺素α和jun的表达相关，HPV16E6通过c-myc基因的E2F基序激活原胸腺素α的表达。结果表明，HPV16E6诱导JUN和ATF2的异源二聚体复合体，随后激活具有CRE基序的基因。综上所述，RA3基因似乎受c-myc或JUN/ATF2的调控，并参与细胞增殖机制。

项目成果

Shino et al.: "Human papillomavirus type 16 E6 protein transcriptionally madulatec fibronactin gene expression by induction of protein complexes" Journal of Virology. (in press).

Shino 等人：“人乳头瘤病毒 16 型 E6 蛋白通过诱导蛋白复合物转录调节纤连蛋白基因表达”病毒学杂志。

Kinoshita et al.: "Transactivotion of prothy mosin-α and c-myc promoters by human papillomavirus type 16 E6 protein" Virology. in press.

Kinoshita 等人：“人乳头瘤病毒 16 型 E6 蛋白对 prothy mosin-α 和 c-myc 启动子的反式激活”病毒学正在出版。

Kinoshita et al.: "Transactivation of prothymosin-α and, c-myc promoters by human papillomavirus type16 E6 protein." Virology. 232. 53-61 (1997)

Kinoshita 等人：“人乳头瘤病毒 16 型 E6 蛋白对胸腺肽原-α 和 c-myc 启动子的反式激活”。232. 53-61 (1997)

Shiga et al.: "Normal human fibroblasts can be immortalized by introduction of human papillomavirus type 16(HPV-16) E6-E7 genes" Microbiology and Immunology. in press.

Shiga 等人：“通过引入人乳头瘤病毒 16 型 (HPV-16) E6-E7 基因，可以使正常人成纤维细胞永生化”微生物学和免疫学。

Kinoshita et al.: "Human papillomavirus type 16E6 protein up-regulates the expression of the high mobility group protein HMG-I(Y)gene in mouse 10T1/2 cells" Virus Research. 42. 119-125 (1996)

Kinoshita 等人：“人乳头瘤病毒 16E6 型蛋白上调小鼠 10T1/2 细胞中高迁移率族蛋白 HMG-I(Y) 基因的表达”病毒研究。