|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1997 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1996 : ¥1,600,000 (Direct Cost : ¥1,600,000)
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.