Transcriptional control in keratinocytes and fibroblasts using synthetic ligands

The Journal of Clinical Investigation
R A FreibergPaul A Khavari

Abstract

The skin is an attractive tissue for regulated target gene expression by virtue of its accessibility to topical regulating stimuli. We have used synthetic ligand-driven intracellular oligomerization to accomplish specific target gene regulation in human skin keratinocytes and fibroblasts. GAL4 DNA binding domains and VP16 transactivation domains, each linked to the FK506 binding protein, were expressed in normal human skin keratinocytes and fibroblasts. These hybrid proteins underwent heterodimerization via the novel intracellular dimerizing agent FK1012 to generate a heterodimeric activator of target gene expression in vitro. Dimeric FK1012, but not monomeric FK506M induced target gene expression in a dose-dependent fashion. FK1012 exerted no detectable nonspecific effects on expression of cutaneous genes and did not alter cellular proliferation kinetics. Controlled oligomerization of hybrid transcription activators offers a potential approach to target gene regulation in cells of normal human skin.

References

Sep 1, 1992·Journal of Cellular Biochemistry·J R PerezK R Cutroneo
Nov 1, 1991·Trends in Genetics : TIG·R Schüle, R M Evans
Nov 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·E S FenjvesL B Taichman
Aug 4, 1988·Nature·M M Davis, P J Bjorkman
Jan 1, 1994·Archives of Dermatological Research·A I LauermaH I Maibach
Nov 12, 1993·Science·D M SpencerG R Crabtree
Jul 16, 1993·Cell·W KolanusB Seed
Feb 1, 1993·Nature Genetics·A J GerrardF M Watt

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Citations

Dec 3, 2002·Current Opinion in Biotechnology·Roy Pollock, Tim Clackson
Oct 24, 1998·Bioorganic & Medicinal Chemistry·T KeenanD A Holt
Sep 24, 2002·Nature Medicine·Susana Ortiz-UrdaPaul A Khavari
Jun 28, 2003·Human Gene Therapy·Susana Ortiz-UrdaPaul A Khavari
Jan 18, 2003·The Journal of Clinical Investigation·Susana Ortiz-UrdaPaul A Khavari
Apr 25, 2007·Annals of Medicine·Thomas G Jensen
Jun 9, 2016·ACS Chemical Biology·Dries J H De ClercqSerge Van Calenbergh
Jun 26, 1999·Journal of Cutaneous Medicine and Surgery·A K SomaniK A Siminovitch

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