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Jumonji regulates cardiomyocyte proliferation via interaction with retinoblastoma protein

Jooyoung Jung1, Tae-Gyun Kim, Gary E Lyons

  • 1Department of Anatomy, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.

The Journal of Biological Chemistry
|May 5, 2005
PubMed

Insights

Jumonji (JMJ) protein represses cell growth by interacting with the retinoblastoma protein (Rb), inhibiting cell cycle progression. This interaction is crucial for normal embryonic development, particularly in heart formation.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Cycle Regulation

Background:

  • Jumonji (JMJ) is a transcriptional repressor involved in embryonic development, including heart development.
  • The precise molecular mechanisms by which JMJ influences cell growth remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying Jumonji's role in cell growth regulation.
  • To investigate the interaction between JMJ and the retinoblastoma protein (Rb) in controlling cell cycle progression.

Main Methods:

  • Co-immunoprecipitation to assess JMJ-Rb interaction.
  • Reporter gene assays to evaluate E2F activity and cell cycle gene promoter activity.
  • Primary cardiomyocyte culture from jmj knock-out mouse embryos.

Main Results:

  • JMJ directly interacts with the retinoblastoma protein (Rb).
  • JMJ enhances Rb-mediated repression of E2F activity, reducing cell cycle progression.
  • jmj knock-out cardiomyocytes exhibit increased mitosis and up-regulated expression of cell cycle regulators (cyclin D1, D2, Cdc2).

Conclusions:

  • JMJ down-regulates cell growth through its interaction with Rb, impacting cell cycle control.
  • These findings provide insights into the cardiac defects observed in jmj mutant mice and highlight JMJ's role in cardiomyocyte proliferation.

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