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.