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Updated: Aug 21, 2026

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH
Published on: August 19, 2014
PML bodies control the nuclear dynamics and function of the CHFR mitotic checkpoint protein
Matthew J Daniels1, Alexander Marson, Ashok R Venkitaraman
1University of Cambridge, Cancer Research UK Department of Oncology and The Medical Research Council Cancer Cell Unit, Hills Road, Cambridge CB2 2XZ, UK.
Abstract:
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.
Insights
The promyelocytic leukemia protein (PML bodies) interact with the CHFR protein, a key player in mitotic checkpoints and cancer. This interaction is crucial for regulating CHFR
Area of Science:
- Cell biology
- Molecular oncology
- Cancer research
Background:
- Nuclear foci containing the promyelocytic leukemia protein (PML bodies) are involved in tumor suppression.
- CHFR is a mitotic checkpoint protein frequently inactivated in human cancers.
Purpose of the Study:
- To investigate the role of PML bodies in the function and localization of the CHFR protein.
- To explore the interaction between CHFR and PML bodies in cancer cells.
Main Methods:
- Intermolecular fluorescence resonance energy transfer (FRET) analysis in living cells.
- Analysis of CHFR and PML distribution and mobility in wild-type and PML-deficient cells.
- Assessment of mitotic entry and response to spindle depolymerization.
Main Results:
- CHFR is a dynamic component of PML bodies, with a fraction of CHFR interacting with PML.
- This interaction influences CHFR's nuclear distribution and mobility.
- A dominant-negative CHFR mutant disrupts colocalization and interaction with PML.
- PML deficiency leads to altered CHFR dynamics, affecting mitotic entry and response to spindle poisons.
Conclusions:
- PML bodies regulate the distribution, dynamics, and function of CHFR.
- The interaction between PML and CHFR is implicated in the cellular response to microtubule-targeting anticancer drugs.
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