Related Experiment Videos
p73 is regulated by phosphorylation at the G2/M transition
Marcella Fulco1, Antonio Costanzo, Paola Merlo
1Laboratory of Gene Expression, Fondazione Andrea Cesalpino, University of Rome "La Sapienza," 00161 Rome, Italy.
The Journal of Biological Chemistry
|August 16, 2003
Summary
The p73 protein, a p53 paralog, is targeted by the p34cdc2-cyclin B kinase during mitosis. This phosphorylation inhibits p73
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- p73 is a p53 paralog with pro- and anti-apoptotic functions.
- TAp73 transcription factors regulate cell cycle arrest, apoptosis, and development.
- p73 protein function is modulated by post-translational modifications and protein interactions.
Purpose of the Study:
- To investigate the role of the p34cdc2-cyclin B mitotic kinase complex in regulating p73.
- To determine how p73 function is affected during mitosis.
Main Methods:
- In vivo studies using normal mitotic cells and cells arrested with microtubule-targeting drugs.
- Analysis of p73 phosphorylation, DNA binding, and transcriptional activity.
- Immunofluorescence to track p73 localization during mitosis.
Main Results:
- p73 (both p73beta and p73alpha isoforms) is hyperphosphorylated by p34cdc2-cyclin B in mitotic cells.
- p34cdc2-cyclin B binds to p73, decreasing its DNA-binding and transcriptional activity.
- p73 is excluded from condensed chromosomes and lacks centrosome association during mitosis.
Conclusions:
- Mitotic phosphorylation of p73 by p34cdc2-cyclin B negatively regulates its transcriptional function.
- This regulation ensures proper cell cycle progression and mitotic events.
- p73 exhibits distinct mitotic behavior compared to p53.