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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/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ#_6 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ#_5 http://www.w3.org/ns/prov#value The cyclin-dependent kinase (CDK) inhibitor p27 is degraded in late G1 phase by the ubiquitin pathway, allowing CDK activity to drive cells into S phase. Ubiquitinylation of p27 requires its phosphorylation at Thr 187 (refs 3, 4) and subsequent recognition by S-phase kinase associated protein 2 (Skp2; refs 5-8), a member of the F-box family of proteins that associates with Skp1, Cul-1 and ROC1/Rbx1 to form an SCF ubiquitin ligase complex. However, in vitro ligation of p27 to ubiquitin could not be reconstituted by known purified components of the SCFSkp2 complex. Here we show that the missing factor is CDK subunit 1 (Cks1), which belongs to the highly conserved Suc1/Cks family of proteins that bind to some CDKs and phosphorylated proteins and are essential for cell-cycle progression. Human Cks1, but not other members of the family, reconstitutes ubiquitin ligation of p27 in a completely purified system, binds to Skp2 and greatly increases binding of T187-phosphorylated p27 to Skp2. Our results represent the first evidence that an SCF complex requires an accessory protein for activity as well as for binding to its phosphorylated substrate. http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ#_5 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/11231585 http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ#_6 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/11231585 http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ#_5 http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ#pubinfo http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ http://purl.org/dc/terms/created 2014-07-03T14:29:54.401+02:00 http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAk0ps9kIVB5vaAewP6okezpXD33YyclYe4dHENfD3azQ http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234