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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
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Hyperglycemia promotes p53-Mdm2 interaction but reduces p53 ubiquitination in RINm5F cells
R Barzalobre-Gerónimo1, Barzalobre-Gerónimo Raúl, L A Flores-López
1Unidad de Investigación Médica en Bioquímica, HE, Centro Médico Nacional Siglo XXI, IMSS, Av Cuauhtémoc 330, Col Doctores, Del. Cuauhtémoc, C.P. 06720, Mexico, DF, Mexico.
Molecular and Cellular Biochemistry
|April 28, 2015
Summary
High glucose levels decrease Mdm2 expression and phosphorylation, leading to reduced p53 ubiquitination and degradation. This stabilization of p53 contributes to pancreatic beta cell loss in hyperglycemia.
Area of Science:
- Cell Biology
- Molecular Biology
- Endocrinology
Background:
- Hyperglycemia-induced beta cell apoptosis is linked to p53.
- Murine double minute 2 (Mdm2) targets p53 for degradation, protecting cells.
Purpose of the Study:
- To investigate how high glucose affects Mdm2's ability to ubiquitinate and degrade p53.
- To understand the role of Mdm2 in p53 stabilization under hyperglycemic conditions.
Main Methods:
- RINm5F cells were cultured with varying glucose concentrations (5 mM or 30 mM).
- Mdm2 mRNA and protein levels were assessed via real-time PCR and Western blotting.
- Phosphorylation of Mdm2, p53, Akt, and ATM was measured.
- p53-Mdm2 complex formation and p53 ubiquitination were analyzed.
Main Results:
- High glucose reduced Mdm2 mRNA and protein expression.
- Mdm2 and Akt phosphorylation increased, while p53 ubiquitination and degradation were suppressed.
- p53-Mdm2 complex formation was enhanced, and p53 Ser15 and ATM phosphorylation increased.
Conclusions:
- High glucose impairs Mdm2's function, leading to p53 stabilization by reducing its ubiquitination.
- This Mdm2-p53 interaction modulation contributes to pancreatic beta cell loss in diabetes mellitus.
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