A Facile and Effective Screening Method for p21WAF1 Promoter Activators from Microbial Metabolites.

• NIE LIN

  Antibiotics Laboratory, RIKEN

• UEKI MASASHI

  Antibiotics Laboratory, RIKEN

• KAKEYA HIDEAKI

  Antibiotics Laboratory, RIKEN

• OSADA HIROYUKI

  Antibiotics Laboratory, RIKEN

抄録

We have developed a novel p21^WAF1 promoter activator screening system based on rapid and facile luciferase activity assay of a model cell system (H1299/tsp53-luc cells), a stable luciferase expression cell line established by transfecting H1299/tsp53 cells with a reporter gene construct pWWP-Luc-BSD. This plasmid was constructed by subcloning the 2.4kb p21^WAF1 promoter and a 2.6kb of luciferase cDNA fragment activated by the p21^WAF1 promoter into a pMAM2-BSD expression vector containing the blasticidin S deaminase gene (BSD). A BSD-resistant clone H1299/tsp53-luc#4, showing the highest response to p53 activation (by temperature shift from 37°C to 32°C) by luciferase production, was used for screening microbial culture broths. Among approximately 1200 screened samples, trichostatin A related compounds and a new compound, lucilactaene, were isolated. This provides an effective and facile screening system for p21^WAF1 promoter activators which should be of considerable value in the rapid identification of new anticancer agents.

収録刊行物

• The Journal of Antibiotics

  The Journal of Antibiotics 54 (10), 783-788, 2001

  公益財団法人 日本感染症医薬品協会

キーワード

• Drug Discovery
• Pharmacology

詳細情報

• CRID: 1390001204149674752
• NII論文ID: 130003503819
• NII論文ID: 50000980561
• NII書誌ID: AA0069330X
• DOI: 10.7164/antibiotics.54.783
• COI: 1:CAS:528:DC%2BD3MXnvF2gs7o%3D
• ISSN: 18811469
• ISSN: 00218820
• PubMed: 11776432
• Web Site: https://search.jamas.or.jp/link/ui/2002118041
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可