Regulating the neoplastic phenotype using engineered transcriptional repressors.
We have applied engineered transcriptional repressors to specifically inhibit disease gene-activated pathways in oncogenesis. We have demonstrated that synthetic repressors combining PAX3 DNA binding domains with different repression domains, KRAB or SNAG, are able to specifically inhibit malignant growth and suppress tumorigenesis in alveolar rhabdomyosarcoma tumor cells transformed by the translocation-derived chimeric transcriptional activator, PAX3-FKHR. We discuss the potential applications of the engineered repressor strategy that relate to target gene analysis, mechanisms of repression, cell regulation, and possible anti-viral and cancer therapy.
Fredericks
W J
WJ
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Ayyanathan
K
K
Rauscher
F J
FJ
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics*; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C068686:Pax3 protein, mouse