p53 negatively regulates Pin1 expression under ER stress.

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• Endoplasmic reticulum (ER) stress is implicated in numerous diseases.
• The apoptotic regulator p53 is upregulated by ER stress, contributing to cell death.
• Mechanisms regulating p53 expression during ER stress require further elucidation.

Purpose of the Study:

• To investigate the role of p53 in regulating Pin1 signaling under ER stress conditions.
• To determine if p53 activation impairs Pin1 expression during ER stress.

Main Methods:

• Treatment of HCT116 cells with thapsigargin to induce ER stress and p53 expression.
• Identification of p53 response elements (p53REs) in the Pin1 promoter.
• Manipulation of p53 expression (overexpression, gene knockout) and activity (p53 inhibitor pifithrin-α).

Main Results:

• Thapsigargin treatment decreased Pin1 expression in HCT116 cells.
• Functional p53REs were identified in the Pin1 promoter.
• p53 overexpression reduced Pin1 expression, while p53 gene abolition increased it.
• Pin1 expression was elevated upon p53 inhibition or downregulation.

Conclusions:

• ER stress diminishes Pin1 expression through p53 activation.
• This p53-mediated downregulation of Pin1 may contribute to ER stress-induced cell death.
• Pin1 emerges as a potential molecular target in tumor development.