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

• Project/Area Number: 08670238
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Chiba University
• Principal Investigator: SHIRASAWA Hiroshi Microbiology I, Chiba University Professor, 医学部, 教授 (00216194)
• Project Period (FY): 1996 – 1997
• Project Status: Completed (Fiscal Year 1997)
• Budget Amount: ¥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)
• Keywords: HPV / E6 / cell proliferation

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kinoshita et al.: "Transactivation of prothymosin-α and c-myc promoters by human papillomavirus type 16E6 protein." Virology. 232. 53-61 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shino et al.: "Human papillomavirus type16E6 protein transcriptionally modulates fibronectin gene expression by induction of protein complexes binding to the CAMP response element" J.Virol.71. 4310-4318 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kinoshita, T., Shirasawa, H., Shino, Y., Shimizu, K., Moriya, H.and Simizu, B: "Human papillomavirus type 16 E6 protein up-regulates the expression of the high mobility group protein HMG-I (Y) gene in mouse 10T1/2 cells." Virus Res.42. 119-125 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kinoshita, T., Shirasawa, H., Shino, Y., Moriya, H., Desbarats, L., Eilers, M.and Simizu, B.: "Transactivation of prothymosin-alpha and c-myc promoters by human papillomavirus type 16 E6 protein." Virology. 232. 53-61 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shino, Y., Shirasawa, H., Kinoshita, T.and Simizu, B.: "Human papillomavirus type 16 E6 protein transcriptionally modulates fibronectin gene expression by induction of protein complexes binding to the cAMP response element." J.Virol.71. 4310-4318 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kinoshita et al: "Human papillomavirus type 16 E6protein up-regulates the expression of the high mobility group protein HMG-I (Y) gene in mouse 10T 1/2 cells :" Virus Research. 42. 119-125 (1996)
• [Publications] Kinoshita et al.: "Transactivation of prothymosin-α and, c-myc promoters by human papillomavirus type16 E6 protein." Virology. 232. 53-61 (1997)
• [Publications] Shino et al: "Human papillomavirus type 16 E6 protein transcriptionally modulates fibronectin gene expression by induction of protein complexes binding to the cAMP response element." J.virol. 71. 4310-4318 (1997)
• [Publications] Kinoshita et al.: "Human papillomavirus type 16 E6 protein up-regulates the expression of the high mobility group protein HMG-I(Y) gene in mouse IOT1/2 cells" Virus Research. 42. 119-125 (1996)
• [Publications] Akutsu et al.: "p53-dependent and-independent traus-activation by the E6 protein of human papillomavirus type 16" Journal of General Virology. 77. 459-463 (1996)
• [Publications] Shimizu et, al.: "Experssion,regulation and polymorphism of the mxil genes." Gene. 176. 45-48 (1996)
• [Publications] 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.
• [Publications] Kinoshita et al.: "Transactivotion of prothy mosin-α and c-myc promoters by human papillomavirus type 16 E6 protein" Virology. in press.
• [Publications] Shino et al.: "Human papillomavirus type 16 E6 protein transcriptionally madulatec fibronactin gene expression by induction of protein complexes" Journal of Virology. (in press).