Related Experiment Videos
ATM is a target for positive regulation by E2F-1
Eli Berkovich1, Doron Ginsberg
1Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
Oncogene
|January 16, 2003
Summary
The transcription factor E2F-1 increases ATM levels and p53 phosphorylation. This reveals a new link between the RB/E2F pathway and p53, impacting cell growth and viability.
Area of Science:
- Molecular Biology
- Cellular Biology
- Cancer Research
Background:
- The RB/E2F pathway regulates cell proliferation, with E2F-1 activation promoting growth.
- Deregulation of E2F-1 can lead to oncogenic stress and apoptosis.
- ATM kinase is crucial for responding to genotoxic stress and activating p53.
Purpose of the Study:
- To investigate the regulatory relationship between E2F-1 and ATM.
- To explore the functional link between the RB/E2F pathway and p53.
Main Methods:
- Analysis of ATM promoter activity.
- Measurement of ATM mRNA and protein levels.
- Assessment of p53 phosphorylation.
- Expression of HPV16 E7 protein to disrupt RB/E2F complexes.
Main Results:
- E2F-1 was found to increase ATM promoter activity, leading to higher ATM mRNA and protein levels.
- E2F-1 also induced increased phosphorylation of p53.
- HPV16 E7 expression mimicked these effects, implicating endogenous E2F.
Conclusions:
- ATM is transcriptionally regulated by E2F-1.
- ATM acts as a novel, ARF-independent link connecting the RB/E2F pathway to p53.
- This interaction influences cell growth control and viability pathways.