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Physical interaction between Wilms tumor 1 and p73 proteins modulates their functions
V Scharnhorst1, P Dekker, A J van der Eb
1Laboratory of Molecular Carcinogenesis and Centre for Biomedical Genetics, Leiden University Medical Center, P. O. Box 9503, 2300 RA Leiden, The Netherlands.
The Journal of Biological Chemistry
|April 1, 2000
Summary
The WT1 gene product interacts with p73 and p63/KET, homologs of p53. These interactions regulate gene transcription, impacting cell growth and differentiation.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- The WT1 gene encodes developmental regulators with four protein isoforms.
- WT1 protein isoforms bind DNA and modulate target gene transcription.
- WT1 interacts with p53, affecting their transcriptional regulation.
Purpose of the Study:
- To investigate the interaction between WT1 protein isoforms and p53 family members.
- To determine the functional consequences of WT1 and p53 family member interactions on transcription.
Main Methods:
- Co-immunoprecipitation assays to detect protein binding.
- Reporter assays to measure transcriptional activity.
- Analysis of endogenous gene expression (Mdm2).
Main Results:
- All four WT1 isoforms bind to p73, a p53 homolog.
- p73 binding inhibits WT1 DNA binding and transcription activation.
- WT1 inhibits p73-induced transcription and Mdm2 expression.
- WT1 also interacts with p63/KET, another p53 homolog.
Conclusions:
- WT1 interacts with p73 and p63/KET, suggesting a role in regulating p53 family functions.
- WT1-p53 family interactions are crucial for cell growth and differentiation control.