A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of a compound library

Gloria H. Su, Taylor A. Sohn, Byungwoo Ryu, Scott E. Kern

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

Libraries of compounds are increasingly becoming commercially available for the use of individual academic laboratories. A high-throughput system based on a stably integrated transcriptional reporter was used to screen a library of random compounds to identify agents that conferred robust augmentation of a signal transduction pathway. A novel histone deacetylase (HDAC) inhibitor, termed scriptaid, conferred the greatest effect, a 12- to 18-fold augmentation. This facilitation of transcriptional events was generally applicable to exogenous gene constructs, including vital and cellular promoters, different cell lines and reporter genes, and stably integrated and transiently introduced sequences. Scriptaid did not interfere with a further induction provided by stimulation of the cognate signal transduction pathway (transforming growth factor β/Smad4), which implied the functional independence of ligand-stimulated transcriptional activation and histone acetylation states in this system. Additional insights into this and other signal transduction systems are likely to be afforded through the application of compound screening technologies.

Original languageEnglish (US)
Pages (from-to)3137-3142
Number of pages6
JournalCancer Research
Volume60
Issue number12
StatePublished - Jun 15 2000
Externally publishedYes

Fingerprint

Histone Deacetylase Inhibitors
Libraries
Signal Transduction
Transforming Growth Factors
Acetylation
Reporter Genes
Histones
Transcriptional Activation
Ligands
Technology
Cell Line
Genes
scriptaid

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of a compound library. / Su, Gloria H.; Sohn, Taylor A.; Ryu, Byungwoo; Kern, Scott E.

In: Cancer Research, Vol. 60, No. 12, 15.06.2000, p. 3137-3142.

Research output: Contribution to journalArticle

Su, Gloria H. ; Sohn, Taylor A. ; Ryu, Byungwoo ; Kern, Scott E. / A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of a compound library. In: Cancer Research. 2000 ; Vol. 60, No. 12. pp. 3137-3142.
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