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Activation-induced nuclear translocation of RING3
1Cancer Research Center, Boston University School of Medicine, Room L910, Boston, MA, USA.
Journal of Cell Science
|August 10, 2000
Summary
RING3 protein kinase regulates cell cycle genes and its nuclear localization is crucial for this function. Dysregulation of RING3 may contribute to human leukaemia development.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- RING3 is a novel protein kinase implicated in human leukaemia.
- Its Drosophila homologue interacts with developmental regulators associated with leukaemia.
- RING3 possesses bromodomains suggesting a role in chromatin remodeling and transcription.
Purpose of the Study:
- To elucidate the mechanism of RING3's function in cell cycle regulation.
- To investigate the role of RING3's nuclear localization in its transcriptional activity.
- To explore the link between RING3 deregulation and leukaemogenesis.
Main Methods:
- Immunostaining and confocal microscopy to track RING3 localization.
- Analysis of nuclear protein complexes involving RING3 and E2F proteins.
- Site-directed mutagenesis to identify the nuclear localization sequence (NLS) of RING3.
Main Results:
- RING3 is constitutively nuclear in HeLa cells but translocates to the nucleus in serum-starved fibroblasts upon stimulation.
- RING3 forms complexes with E2F proteins and transactivates E2F-dependent cell cycle genes.
- A classical NLS is essential for RING3's serum-stimulated nuclear import and transcriptional activity.
Conclusions:
- RING3's activity is regulated by its nuclear localization, dependent on a classical NLS.
- RING3 plays a significant role in E2F-mediated cell cycle progression.
- Disruption of this pathway may underlie leukaemogenesis.