p53 isoforms have a high aggregation propensity, interact with chaperones and lack binding to p53 interaction...

Area of Science:

• Molecular Biology
• Cancer Research
• Protein Biochemistry

Background:

• The p53 transcription factor family includes p53, p63, and p73.
• p63 and p73 have well-characterized isoforms.
• p53 isoforms are implicated in increased cancer metastasis.

Purpose of the Study:

• To biochemically characterize p53 isoforms.
• To understand the role of p53 isoforms in cancer progression.

Main Methods:

• Biochemical characterization of p53 variants.
• Analysis of DNA-binding affinity and transcriptional activity.
• Interaction studies using antibodies and DARPins.
• Chaperone protein expression analysis.

Main Results:

• Most p53 isoforms, except Δ40p53α, exhibit low DNA-binding affinity and do not upregulate transcription.
• p53 isoforms with deletions in the DNA-binding domain (DBD) do not interact with specific partners but bind to chaperones.
• Expression of DBD-deleted p53 isoforms leads to chaperone upregulation.
• High expression levels cause p53 isoform aggregation and co-aggregation.

Conclusions:

• p53 isoforms with DBD deletions are functionally impaired in DNA binding and transcription.
• These isoforms interact with chaperones, leading to aggregation when expressed at high levels.
• The aggregation of p53 isoforms may contribute to cancer progression and metastasis.