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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4#_6 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4#_5 http://www.w3.org/ns/prov#value Orlistat reduced phosphorylation of the Rb protein, up-regulated p27Kip1, and down-regulated Skp2. These effects were evident at levels of the drug consistent with the cellular IC50 of Orlistat for inhibition of the FAS thioesterase (1-3 M). To independently verify that the effects of Orlistat could be attributed to its ability to block FAS, similar experiments were conducted with siRNA-targeting FAS (Fig. 4B). Like Orlistat, the siRNA-targeting FAS decreased the phosphorylation of Rb, increased the level of p27Kip1, and reduced the level of Skp2. An siRNA-targeting Skp2 had identical effects upon its downstream target, p27Kip1, and upon the phosphorylation status of the Rb protein. Together, these findings provide strong support for the idea that a FAS blockade acts upon the Rb pathway via regulation of Skp2 and also indicate that a FAS blockade is likely to have effects similar to an Skp2 blockade. http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4#_5 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/15138278 http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4#_6 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/15138278 http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4#_5 http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4#pubinfo http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4 http://purl.org/dc/terms/created 2014-07-03T14:30:23.303+02:00 http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4 http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAZgUs3c-6Uja81VH2QfWntUOp_7Sc0VALa_Bck9URzX4 http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234