Functional analysis of tumor suppressor p53 protein regulated by ubiquitin-proteasome system

Yoichi Nagata, Tadashi Anan, Yoshiomi Honda, Reiji Kimura, Hidevuki Saya, Mitsuvoshi Nakao, Motomi Nakata, Naoki Shinbara, Keiii Tanaka, Satoshi Omura

研究成果: Article

抜粋

The tumor suppressor p53 protein is most important for cell regulation such as cell cycle and apoptosis. In HPV-infected cells including HeLa cells, a viral oncpprptein E6 and a cellular E6-associated protein (E6AP) function together as a ubiquitin ligase targetting for p53. The complex plays a major role in the tumorigenesis by rapid turnover of p53. However, the mechanism of p53 degradation in normal cells remains unclear. 1) Using proteasome inhibitors, p53 protein was significantly accumulated in primary nbroblasts as well as HeLa cells in vivo. 2) Recombinant p53 proteins destined for wild- or mutant(273His)-type were analysed in an appropriate buffer and rabbit reticulpcyte lysates in vitro. Much slower degradation of mutant-p53 was found compared with the case of wild-p53. Interestingly, bpth-types of p53 were multiubiquitinated in a similar manner. 3) In fibroblasts infected with p53-expressing adenovirus, wild-p53 protein was co-immunoprecipitated with anti-E6AP antibody. In summary, E6AP may also work in the p53 ubiquitination in normal cells adding to E6-dependent case. Uoiguitinated mutant-p53 becomes resistant to degradation, suggesting that mutant-p53 is hardly recognized and/or degraded by proteasome due to unknown mechanism.

元の言語English
ページ数1
ジャーナルJapanese Journal of Human Genetics
42
発行部数1
出版物ステータスPublished - 1997 12 1
外部発表Yes

ASJC Scopus subject areas

  • Genetics(clinical)

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  • これを引用

    Nagata, Y., Anan, T., Honda, Y., Kimura, R., Saya, H., Nakao, M., Nakata, M., Shinbara, N., Tanaka, K., & Omura, S. (1997). Functional analysis of tumor suppressor p53 protein regulated by ubiquitin-proteasome system. Japanese Journal of Human Genetics, 42(1).