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http://purl.uniprot.org/citations/23707388http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23707388http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23707388http://www.w3.org/2000/01/rdf-schema#comment"Cell cycle progression through its regulatory control by changes in intracellular Ca(2+) levels at the G1/S transition mediates cellular proliferation and viability. Ca(2+)/CaM-dependent kinase 1 (CaMKI) appears critical in regulating the assembly of the cyclin D1/cdk4 complex essential for G1 progression, but how this occurs is unknown. Cyclin D1/cdk4 assembly in the early G1 phase is also regulated via binding to p27. Here, we show that a ubiquitin E3 ligase component, F-box protein Fbxl12, mediates CaMKI degradation via a proteasome-directed pathway leading to disruption of cyclin D1/cdk4 complex assembly and resultant G1 arrest in lung epithelia. We also demonstrate that i) CaMKI phosphorylates p27 at Thr(157) and Thr(198) in human cells and at Thr(170) and Thr(197) in mouse cells to modulate its subcellular localization; ii) Fbxl12-induced CaMKI degradation attenuates p27 phosphorylation at these sites in early G1 and iii) activation of CaMKI during G1 transition followed by p27 phosphorylation appears to be upstream to other p27 phosphorylation events, an effect abrogated by Fbxl12 overexpression. Lastly, known inducers of G1 arrest significantly increase Fbxl12 levels in cells. Thus, Fbxl12 may be a previously uncharacterized, functional growth inhibitor regulating cell cycle progression that might be used for mechanism-based therapy."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.org/dc/terms/identifier"doi:10.1016/j.cellsig.2013.05.012"xsd:string
http://purl.uniprot.org/citations/23707388http://purl.org/dc/terms/identifier"doi:10.1016/j.cellsig.2013.05.012"xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Zhao J."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Zhao J."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Chen B.B."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Chen B.B."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Agassandian M."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Agassandian M."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Mallampalli R.K."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Mallampalli R.K."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Coon T."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Coon T."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Kaercher L."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Kaercher L."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Pulijala R."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Pulijala R."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Snavely C."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/author"Snavely C."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/name"Cell. Signal."xsd:string
http://purl.uniprot.org/citations/23707388http://purl.uniprot.org/core/name"Cell. Signal."xsd:string