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PMID:15870077

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Citation

Jung, J, Kim, TG, Lyons, GE, Kim, HR and Lee, Y (2005) Jumonji regulates cardiomyocyte proliferation via interaction with retinoblastoma protein. J. Biol. Chem. 280:30916-23

Abstract

Jumonji (JMJ) can function as a transcriptional repressor and plays critical roles in embryonic development including heart development in mice. Although JMJ has been suggested to play a role in cell growth, the molecular mechanisms have not been resolved. The present data demonstrate that JMJ interacts with the retinoblastoma protein (Rb), one of the master regulatory genes of cell cycle. JMJ potentiates the repression function of Rb on E2F activities, leading to reduced cell cycle progression. The transcriptional repression domain of JMJ is critical for the interaction with Rb as well as repression of cell cycle. The physiological relevance of the association between Rb and JMJ was assessed in cardiomyocytes. Primary cardiomyocytes cultured from homozygous jmj knock-out mouse embryos (jmj mutants) show increased cell mitosis in a cardiomyocyte-specific manner. Reporter gene analyses demonstrate that promoter activities of cyclin D1, cyclin D2, and Cdc2 are up-regulated in jmj mutant cardiomyocytes. These data suggest that JMJ down-regulates the cell growth via interaction with Rb, which would provide important insights into the cardiac defects observed in jmj mutant mice.

Links

PubMed Online version:10.1074/jbc.M414482200

Keywords

Animals; Cell Cycle/physiology; Cell Proliferation; Cells, Cultured; Cyclin D1/metabolism; Cyclin D2; Cyclins/metabolism; Embryo, Mammalian/anatomy & histology; Embryo, Mammalian/physiology; Gene Expression Regulation; Genes, Reporter; Humans; Mice; Myocytes, Cardiac/cytology; Myocytes, Cardiac/physiology; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Phenotype; Promoter Regions, Genetic; Protein Structure, Tertiary; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Retinoblastoma Protein/genetics; Retinoblastoma Protein/metabolism

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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