ISOLATION AND CHARACTERIZATION OF AXOLOTL NPDC-1 AND ITS EFFECTS ON RETINOIC ACID RECEPTOR SIGNALING

Comp Biochem Physiol B Biochem Mol Biol, 2007 · DOI: 10.1016/j.cbpb.2007.01.008 · Published: June 1, 2007

Simple Explanation

This study focuses on NPDC-1, a protein that interacts with retinoic acid receptors (RARs). Retinoic acid is important for development and tissue regeneration. The researchers cloned the axolotl version of NPDC-1 to compare it to the mammalian version. They wanted to understand NPDC-1's role in regulating retinoic acid signaling. The study found that axolotl NPDC-1 interacts with axolotl RAR, affects how RAR binds to DNA, and suppresses cell growth and transcription controlled by RAR.

Study Duration

Not specified

Participants

Axolotl embryos and juvenile axolotls, HEK293 and Cos7 cells

Evidence Level

In vitro and cell-based experiments

Key Findings

1
Axolotl NPDC-1 mRNA expression peaks late in embryogenesis, coinciding with limb development, a process regulated by retinoic acid.
2
Axolotl NPDC-1 directly interacts with axolotl RAR, modulates axolotl RAR DNA binding, and represses cell proliferation and axolotl RAR-mediated gene transcription.
3
A novel NPDC-1-specific higher mobility shift complex was observed in axolotl, suggesting a unique interaction compared to mammals.

Research Summary

The study isolated and characterized the axolotl orthologue of NPDC-1, a co-regulatory protein involved in retinoic acid signaling. Axolotl NPDC-1 shares structural and functional similarities with its mammalian counterparts, including interaction with RAR, modulation of DNA binding, and repression of transcription and cell proliferation. The study provides evidence for a conserved role of NPDC-1 in retinoic acid signaling during chordate development, extending from humans to axolotls.

Practical Implications

Model Organism

Justifies axolotl as a model to further investigate NPDC-1 and its role in regulating retinoic acid signaling.

Understanding Development

Provides insights into the regulation of retinoic acid signaling during limb development and embryogenesis.

Drug Development

Potential for developing therapeutic strategies targeting NPDC-1 and retinoic acid signaling in diseases involving cell proliferation and differentiation.

Study Limitations

1
Low sequence similarity between axolotl and mammalian NPDC-1 orthologues.
2
Use of human RXR isoform due to lack of cloned axolotl RXR.
3
Expression of axolotl proteins in mammalian cells for in vitro transcription analysis.

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