Abstract
The p53 pathway is a central apoptotic regulator. Deregulation of the Rb/E2F pathway occurs in a majority of tumors, resulting in both unrestrained proliferation and enhanced apoptosis sensitivity via p53-dependent and independent mechanisms. However, the mechanisms coupling the p53 and Rb/E2F pathways remain incompletely understood. We report that ASPP2/53BP2L, a p53/p73-binding protein that promotes p53/p73-dependent apoptosis, is an E2F target gene. The ASPP2/53BP2L promoter was identified and ectopic expression of transcription-competent E2F-1 (E2F-2 and E2F-3) stimulated an ASPP2/53BP2L promoter-luciferase reporter. Mutational analysis of the ASPP2/53BP2L promoter identified E2F-binding sites that cooperate for E2F-1 induction and basal repression of ASPP2/53BP2L. Moreover, endogenous ASPP2/53BP2L levels increased after E2F-1 expression, and E2F-1 bound the endogenous ASPP2/53BP2L promoter after chromatin immunoprecipitation. Typical for an E2F target, ASPP2/53BP2L expression was maximal in early S-phase. Thus, ASPP2/53BP2L is downstream of E2F, suggesting that it functions as a common link between the p53/p73 and Rb/E2F apoptotic pathways.
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Abbreviations
- ChIP:
-
chromatin immunoprecipitation
- FBS:
-
fetal bovine serum
- β-gal:
-
β-galactosidase
- HU:
-
hydroxyurea
- luc:
-
luciferase
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Acknowledgements
This work was supported by funds from the OHSU Cancer Institute/OHSU Foundation, and from PHS-NIH K08-CA85773 and 1R01-CA104997-01A1 to CDL.
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Chen, D., Padiernos, E., Ding, F. et al. Apoptosis-stimulating protein of p53-2 (ASPP2/53BP2L) is an E2F target gene. Cell Death Differ 12, 358–368 (2005). https://doi.org/10.1038/sj.cdd.4401536
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DOI: https://doi.org/10.1038/sj.cdd.4401536
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