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PCAF is a coactivator for p73-mediated transactivation.
Lisa Y Zhao1, Yue Liu, Nicholas R Bertos
1Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610-0235, USA.
Oncogene
|November 14, 2003
Summary
The p73 protein interacts with the PCAF coactivator, which is essential for p73
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- The tumor suppressor p73 is structurally and functionally similar to p53.
- Both p53 and p73 interact with transcription coactivators like p300/CBP.
- The role of coactivators in p73-mediated gene regulation is not fully understood.
Purpose of the Study:
- To investigate the interaction between p73 and the coactivator PCAF.
- To determine the functional significance of the p73-PCAF interaction in gene transcription and cellular processes.
Main Methods:
- Co-immunoprecipitation assays to study protein-protein interactions.
- Western blotting and quantitative PCR to assess gene expression.
- RNA interference (siRNA) to knock down PCAF expression.
- Cell-based assays for apoptosis and colony formation.
Main Results:
- PCAF binds to p73, requiring specific domains in both proteins (p73's TAD and OD; PCAF's HAT domain).
- PCAF significantly enhances p73-mediated transactivation of target genes, such as p21.
- PCAF depletion using siRNA reduces p73's transcriptional activity.
- Coexpression of PCAF and p73 promotes apoptosis and inhibits colony formation.
Conclusions:
- PCAF acts as a critical coactivator for p73, enhancing its transcriptional activity.
- The p73-PCAF complex recruits PCAF to target gene promoters, like the p21 promoter.
- This interaction plays a significant role in p73-induced apoptosis and tumor suppression.