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Published on: August 21, 2013
Mortalin controls centrosome duplication via modulating centrosomal localization of p53
1Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0521, USA.
Oncogene
|April 19, 2006
Summary
Abnormal centrosome amplification in cancer is linked to mortalin, a heat shock protein. Mortalin interacts with p53, promoting centrosome duplication and overriding p53-dependent suppression.
Area of Science:
- Cell Biology
- Cancer Biology
- Molecular Biology
Background:
- Abnormal centrosome amplification is a hallmark of human cancer, leading to mitotic defects and chromosome instability.
- Centrosome duplication, normally occurring once per cell cycle, is tightly regulated.
- Defects in this regulation result in centrosome amplification and associated pathologies.
Purpose of the Study:
- To identify proteins associated with duplicated centrosomes.
- To elucidate the role of identified proteins in regulating centrosome duplication.
- To investigate the interaction between mortalin and p53 in centrosome regulation.
Main Methods:
- Comparative mass spectrometric analysis of unduplicated and duplicated centrosomes.
- Immunofluorescence microscopy to determine protein localization during the cell cycle.
- Overexpression studies and analysis of p53 mutants to assess functional interactions.
Main Results:
- Mortalin, a heat shock protein, was identified as preferentially associating with duplicated centrosomes.
- Mortalin localizes to centrosomes from late G1 through G2 and dissociates during mitosis.
- Mortalin overexpression overrides p53-dependent suppression of centrosome duplication via physical interaction with p53, promoting p53 dissociation from centrosomes.
Conclusions:
- Mortalin is an upstream regulator of p53 in the context of centrosome duplication.
- Centrosomally localized p53 plays a role in suppressing centrosome duplication.
- Findings reveal a novel mechanism involving mortalin and p53 in controlling centrosome duplication, relevant to cancer development.
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