Phorboxazole analogues induce association of cdk4 with extranuclear cytokeratin intermediate filaments.
The cellular localization profile and molecular association of the phorboxazoles were examined with a streamlined target elucidation system using synthetic fluorescent probes. Cellular image analyses identified the binding of phorboxazole analogues to cytosolic components. Proteomic analysis directed at fluorescently labeled cytosolic fractions indicated that the primary targets observed microscopically were cytokeratins, as verified by determination of low nanomolar binding to cloned and expressed proteins. Phorboxazole probes localized the essential cell cycle promoter cdk4 upon cytokeratin networks.
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA. forsyth@chem.umn.edu
Craig J
CJ
Forsyth
Lu
L
Ying
Jiehao
J
Chen
James J
JJ
La Clair
D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D051358:Cyclin-Dependent Kinase 4 / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007382:Intermediate Filaments / Q000737:chemistry* / Q000378:metabolism; D007633:Keratins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008856:Microscopy, Fluorescence; D010080:Oxazoles / Q000737:chemistry* / Q000494:pharmacology
D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; D007633:Keratins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4