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

应用差异杂交技术克隆了人乳头瘤病毒16型(HPV16)E6蛋白影响的细胞基因。三分之二的克隆是那些在细胞周期中调节的克隆，如HMG-IY(高迁移率族蛋白-I[Y])、胸腺素原-α或鸟氨酸脱羧酶。一个未知的克隆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的表达解除了对RA3表达的抑制。RA3的全长为1.3kb，与其他已知基因没有同源性。RA3基因的表达与胸腺素α原和JUN的表达相关，HPV16E6通过c-myc基因的E2F基序激活胸腺素α原的表达。结果表明，在HPV16E6的作用下，Jun与ATF2形成异二聚体复合体，激活具有Cre基序的基因，RA3基因可能受c-myc或Jun/ATF2的调控，参与细胞增殖的机制。

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.