Detection of novel molecules that regulates RB expression by screening random peptide library

通过筛选随机肽库检测调节RB表达的新分子

• 批准号: 05454178
• 负责人: TAKAHASHI Rei
• 金额: $ 3.33万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454178/
• 关键词: peptide library; tumor suppressor gene; RB; p53; promoter; enhancer; RB遺伝子; 転写調節; サイレンサー

Inactivation of the RB gene is one of the authentic models for carcinogenesis in tumor suppressor genes. Not only intragenic mutations but also inactivation of promoter activity by mutation or other epigenetic factors are of important factors that regulate expression of the RB gene. In this study, we try to elucidate mechanisms involved in such regulation of the promoter region of the RB gene by screening random peptides that were created by a phage library. we have isolated several clones which express peptide sequence binding to the RB promoter. The structural analysis including three dimensional construction will be performed to obtain structural basis for the interaction between the elements and the isolated peptide sequences. On the other hand, we also found a region in the RB promoter that can interact with a silencer molecule.

Rb基因失活是肿瘤抑制基因致癌的可靠模型之一。不仅基因内突变，而且突变或其他表观遗传因素导致的启动子活性失活也是调控Rb基因表达的重要因素。在这项研究中，我们试图通过筛选噬菌体文库产生的随机多肽来阐明参与Rb基因启动子区调控的机制。我们已经分离到几个表达与Rb启动子结合的肽序列的克隆。将进行结构分析，包括三维结构，以获得元件与分离的多肽序列相互作用的结构基础。另一方面，我们还在RB启动子中发现了一个可以与消音剂分子相互作用的区域。

项目成果

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Ohtani-Fujita Naoko：“视网膜母细胞瘤肿瘤抑制基因中的沉默元件”Oncogene。

Tamura Takao: "Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells" Oncogene. 11. 1939-1946 (1995)

Tamura Takao：“在 p53 转染的人结肠癌细胞中诱导 Fas 介导的细胞凋亡”Oncogene。

Osifchin N. E.: "Identification of a p53 binding site in the human retinoblastoma susceptibility gene promoter" The Journal of Biological Chemistry. 269. 6383-6389 (1994)

Osifchin N. E.：“人视网膜母细胞瘤易感基因启动子中 p53 结合位点的鉴定”《生物化学杂志》。

Inagaki T.: "Establishment of human oral-cancer cell lines(KOSC-2 and-3)carrying p53 and c-myc abnormalities by Geneticin treatment" International Journal of Cancer. 56. 301-308 (1994)

Inagaki T.：“通过遗传霉素治疗建立携带 p53 和 c-myc 异常的人类口腔癌细胞系（KOSC-2 和-3）”国际癌症杂志。

Savoysky E.: "The retinoblastoma binding factor 1(RBF-1)site in RB gene promoter binds preferentially E4TF1, a member of the Ets transcription factors family" Oncogene. 9. 1839-1846 (1994)

Savoysky E.：“RB 基因启动子中的视网膜母细胞瘤结合因子 1 (RBF-1) 位点优先结合 E4TF1，E4TF1 是 Ets 转录因子家族的成员”Oncogene。