Tracing MYC Expression for Small Molecule Discovery.
Cell Chem Biol
; 26(5): 699-710.e6, 2019 05 16.
Article
en En
| MEDLINE
| ID: mdl-30880156
ABSTRACT
Our inability to effectively "drug" targets such as MYC for therapeutic purposes requires the development of new approaches. We report on the implementation of a phenotype-based assay for monitoring MYC expression in multiple myeloma cells. The open reading frame (ORF) encoding an unstable variant of GFP was engineered immediately downstream of the MYC ORF using CRISPR/Cas9, resulting in co-expression of both proteins from the endogenous MYC locus. Using fluorescence readout as a surrogate for MYC expression, we implemented a pilot screen in which â¼10,000 compounds were prosecuted. Among known MYC expression inhibitors, we identified cardiac glycosides and cytoskeletal disruptors to be quite potent. We demonstrate the power of CRISPR/Cas9 engineering in establishing phenotype-based assays to identify gene expression modulators.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Transcripción Genética
/
Proteínas Proto-Oncogénicas c-myc
/
Bibliotecas de Moléculas Pequeñas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá