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Functional interplay between p53 and E2F through co-activator p300
C W Lee1, T S Sørensen, N Shikama
1Division of Biochemistry and Molecular Biology, University of Glasgow, UK.
Oncogene
|July 4, 1998
Summary
The co-activator p300 influences cell fate by interacting with transcription factors E2F and p53. p300 directs p53 to induce cell cycle arrest or apoptosis, impacting cancer progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- E2F and p53 are transcription factors regulating cell cycle progression.
- p53 responds to genotoxic stress by inducing cell cycle arrest or apoptosis.
- The mechanisms governing p53's cellular outcome are not fully understood.
Purpose of the Study:
- To identify co-activators involved in p53-dependent transcription.
- To elucidate the role of p21(Waf1/Cip1) in regulating p53 and E2F activity.
- To investigate how p300 influences the interplay between p53 and E2F pathways.
Main Methods:
- Biochemical assays
- Functional assays
- Analysis of gene transcription
- Assessment of cell cycle progression (G1 arrest) and apoptosis
Main Results:
- p300 acts as a co-activator for p53-dependent transcription of Waf1/Cip1.
- p21(Waf1/Cip1) autoregulates p53/p300 activity and inhibits E2F activity.
- p300 enhances p53-mediated G1 arrest and rescues cells from p53-dependent apoptosis.
- p300 enhances E2F-1-induced apoptosis and can be competed for by E2F-1 during co-operative apoptosis.
Conclusions:
- p300 plays a critical role in determining the outcome of p53 activation, directing cells towards arrest or apoptosis.
- p300 integrates the functional interplay between E2F and p53 pathways.
- The interaction of p300 with p53 or E2F-1 profoundly impacts early cell cycle control, balancing cell cycle arrest and apoptosis.