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10:55
Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
Monoubiquitylation promotes mitochondrial p53 translocation.
Natasha D Marchenko1, Sonja Wolff, Susan Erster
1Department of Pathology, Stony Brook University, Stony Brook, New York, NY 11794-869, USA.
The EMBO Journal
|February 3, 2007
Summary
Stress stabilizes p53 in the cytoplasm, promoting its mitochondrial translocation for apoptosis. Mdm2-mediated monoubiquitylation facilitates this, while mitochondrial HAUSP deubiquitylation activates p53.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The p53 tumor suppressor induces apoptosis via transcription-dependent and -independent pathways.
- p53 plays a direct role in mitochondrial apoptosis, but its delivery mechanism to mitochondria is unclear.
Purpose of the Study:
- To elucidate the mechanism of p53 delivery to mitochondria upon stress-induced stabilization.
- To investigate the role of ubiquitylation in p53 mitochondrial translocation and apoptosis.
Main Methods:
- Analysis of p53 ubiquitylation status and subcellular localization under stress.
- Manipulation of Mdm2 and HAUSP activity to assess their impact on p53 function.
- Biochemical assays to study p53-Mdm2 and p53-HAUSP interactions.
Main Results:
- A distinct cytoplasmic p53 pool is the primary source for mitochondrial translocation.
- Mdm2-mediated monoubiquitylation enhances p53 mitochondrial targeting and apoptosis.
- Mitochondrial HAUSP deubiquitylates p53, generating the active, non-ubiquitylated form.
Conclusions:
- A novel model for mitochondrial p53 targeting is proposed, involving Mdm2-dependent monoubiquitylation and HAUSP-mediated deubiquitylation.
- This mechanism regulates the balance between p53 degradation and activation for apoptosis.
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