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Updated: Aug 8, 2026
08:01
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Hrt and Hes negatively regulate Notch signaling through interactions with RBP-Jkappa
Isabelle N King1, Irfan S Kathiriya, Masao Murakami
1Department of Pediatrics, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9063, USA. iking@gladstone.ucsf.edu
Biochemical and Biophysical Research Communications
|May 10, 2006
Summary
Hrt2 and Hes1 proteins negatively regulate Notch signaling by interacting with RBP-Jkappa. This novel feedback mechanism involves Hrt and Hes acting as co-repressors, impacting gene expression in cardiovascular development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Signaling
Background:
- Notch signaling is crucial for cell differentiation and organ development.
- Notch signaling regulates target genes via the NotchIC-RBP-Jkappa complex.
- Hrt and Hes families are basic-helix-loop-helix (bHLH) transcriptional repressors involved in development.
Purpose of the Study:
- To investigate the role of Hrt2 and Hes1 in Notch signaling regulation.
- To elucidate the mechanism of negative feedback on Notch-dependent gene expression.
Main Methods:
- Investigated protein-protein interactions using co-immunoprecipitation assays.
- Assessed the impact of these interactions on gene expression.
- Utilized mice models with genetic modifications (Hrt2 deficiency).
Main Results:
- Hrt2 and Hes1 directly interact with RBP-Jkappa.
- This interaction negatively regulates Notch-dependent activation of Hrt and Hes expression.
- The bHLH domain of Hrt2 is essential for this interaction.
- Disruption of the Hrt2-RBP-Jkappa complex abolished negative autoregulation.
- Hrt2 and Hes1 function as co-repressors without interfering with NotchIC-RBP-Jkappa complex formation or DNA binding.
Conclusions:
- Identified a novel negative feedback loop in Notch signaling.
- Hrt and Hes proteins act as RBP-Jkappa-dependent co-repressors.
- This mechanism provides precise control over Notch target gene expression, particularly in cardiovascular development.
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