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 viral 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 beta/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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Su GH,Sohn TA,Ryu B,Kern SEsubject
Has Abstractpub_date
2000-06-15 00:00:00pages
3137-42issue
12eissn
0008-5472issn
1538-7445journal_volume
60pub_type
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