| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1999: ¥7,500,000 (Direct Cost: ¥7,500,000)
|
|---|
| Research Abstract |
p53 tumor suppressor gene, sensing DNA damage, causes cells to undergo G1-arrestor apoptotic death, thereby playing a critical role in human carcinogenesis. Searching for p53 related genes, I successfully isolated p51 along with p73. In addition to their structural resemblance, they exhibited functional similarities to p53. I obtained following result by analyses of p53 family genes. (1) Analyses using chimeric gene constructs : Chimeric genes composed of p51, p53, and p73 coding sequences by connecting their major functional domains, proved to have striking preference over various promoters with variety of properties. In an attempt to take advantage of these properties suitable for gene therapeutic application and functional analyses, I constructed adenoviral version. (2) Analyses of genomic p51 and p73 : Genomic sequencing analyses of nearly entire of p51 and p73, revealed striking similarity. Two independent promoter regions of p51, TAp51 andΔNp51 promoters, were identified. I also started to clone and/or analyze transactivtor gene responsible for transcription of ΔNp51, since the ΔNp51 promoter was narrowed down to two 10 bp regions. (3) Analyses of newly identified isoforms : I newly identified various isoforms of p51 and p73. Most importantly of ΔNp73, which proved to exert dominant negative function against TAp73 and p53. (4) Analyses of p51, p73 protein regulation : I found that p51 was not regulated by MDM2, a major regulator of p53 protein activity. Nevertheless, observation of strong ubiquitination of p51 led us to investigate and clone MDM2-like gene capable of regulating p51.
|
