Apoptosis-stimulating protein of p53-2 (ASPP2/53BP2L) is an E2F target gene.
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.
Chen
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Department of Medicine, Division of Hematology and Medical Oncology, L586B, Oregon Health & Science University, Portland, OR 97239, USA.
Padiernos
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Ding
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Lossos
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Lopez
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D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; D005786:Gene Expression Regulation / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016196:S Phase / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D050699:E2F3 Transcription Factor; D009687:Nuclear Proteins; C090468:TP53BP2 protein, human; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins