Nature Structural & Molecular Biology11, 1114 - 1121 (2004)
Published online: 3 October 2004; | doi:10.1038/nsmb837
PML bodies control the nuclear dynamics and function of the CHFR mitotic checkpoint protein
Matthew J Daniels, Alexander Marson
& Ashok R Venkitaraman
University of Cambridge, Cancer Research UK Department of Oncology and The Medical Research Council Cancer Cell Unit, Hills Road, Cambridge CB2 2XZ, UK.
Correspondence should be addressed to Ashok R Venkitaraman arv22@cam.ac.uk
Nuclear foci containing the promyelocytic leukemia protein (PML bodies), which occur in most cells, play a role in tumor suppression. Here, we demonstrate that CHFR, a mitotic checkpoint protein frequently inactivated in human cancers, is a dynamic component of PML bodies. Intermolecular fluorescence resonance energy transfer analysis identified a distinct fraction of CHFR that interacts with PML in living cells. This interaction modulates the nuclear distribution and mobility of CHFR. A trans-dominant mutant of CHFR that inhibits checkpoint function also prevents colocalization and interaction with PML. Conversely, the distribution and mobility of CHFR are perturbed in PML-/- cells, accompanied by aberrations in mitotic entry and the response to spindle depolymerization. Thus, PML bodies control the distribution, dynamics and function of CHFR. Our findings implicate the interaction between these tumor suppressors in a checkpoint response to microtubule poisons, an important class of anticancer drugs.
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