The membrane-bound transcription factor ATF6α plays a cytoprotective role in the unfolded protein response (UPR), required for cells to survive ER stress. Activation of ATF6α promotes cell survival in cancer models. We used cell-based screens to discover and develop Ceapins, a class of pyrazole amides, that block ATF6α signaling in response to ER stress.
View Article and Find Full Text PDFBackground: Analysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the "driver" gene(s) within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21-1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp12).
View Article and Find Full Text PDFThe fibroblast growth factor (vfgf) gene encoded by Autographa californica M nucleopolyhedrovirus (AcMNPV) has been shown to share functional properties with cellular fgfs; it is a secreted protein, binds heparin, and stimulates motility of insect cells. We previously reported that viruses containing or lacking vfgf produced similar yields of budded virus and had similar kinetics of viral DNA and protein syntheses in cultured cells. In this study, we characterized these viruses in two permissive hosts, Spodoptera frugiperda and Trichoplusia ni, using two insect developmental stages and two infection routes, by feeding and intrahemocoelic injection.
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