ASPP Proteins Specifically Stimulate the Apoptotic Function of p53
Open accessAbstract
We identified a family of proteins termed ASPP. ASPP1 is a protein homologous to 53BP2, the C-terminal half of ASPP2. ASPP proteins interact with p53 and specifically enhance p53-induced apoptosis but not cell cycle arrest. Inhibition of endogenous ASPP function suppresses the apoptotic function of endogenous p53 in response to apoptotic stimuli. ASPP enhance the DNA binding and transactivation function of p53 on the promoters of proapoptotic genes in vivo. Two tumor-derived p53 mutants with reduced apoptotic function were defective in cooperating with ASPP in apoptosis induction. The expression of ASPP is frequently downregulated in human breast carcinomas expressing wild-type p53 but not mutant p53. Therefore, ASPP regulate the tumor suppression function of p53 in vivo.
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p53 activators JMY, TOPORS, TP53BP2, DAXX, and HNRPK can stabilize p53 protein levels by interfering with MDM2 and/or act as p53 transcriptional cofactors, assisting p53 in transactivating genes that induce apoptosis and growth arrest.
“The miR-21 targets we identified included p53 homologue, p63, p53 activators JMY, TOPORS, TP53BP2, DAXX, and HNRPK, which can stabilize p53 protein levels by interfering with MDM2 and/or act as p53 transcriptional cofactors, assisting p53 in transactivating genes that can induce apoptosis and growth arrest (21)(22)(23)(24)(25)(26).”
From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [23]
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Self-citation
- Authors
- Samuels-Lev, Y., O'Connor, D. J., Bergamaschi, D., Trigiante, G., Hsieh, J.-K., Zhong, S., Campargue, I., Naumovski, L., Crook, T., & Lu, X.
- Affiliations
- Ludwig Cancer Research (GB)
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 8
- Issue
- 4
- Pages
- 781-794
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2087732778
- Cited by
- 664
- References
- 22
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 15 · 2023: 20 · 2022: 16 · 2021: 26 · 2020: 13 · 2019: 20 · 2018: 8 · 2017: 27 · 2016: 18 · 2015: 23 · 2014: 37 · 2013: 35 · 2012: 31
- FWCI
- 13.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- ASPP1, ASPP2, p53, apoptosis, p53 DNA binding, p53 transactivation, tumor suppression, breast cancer, mutant p53, cell cycle arrest
- MeSH terms
- Breast Neoplasms, Carcinoma, Carrier Proteins, Cell Separation, Female, Flow Cytometry, Humans, Microscopy, Fluorescence, Molecular Sequence Data, Peptide Fragments, Promoter Regions, Genetic, Proto-Oncogene Proteins, Tumor Cells, Cultured, Transcriptional Activation, Tumor Suppressor Protein p53, Cyclins, Apoptosis, Protein Structure, Tertiary, Proto-Oncogene Proteins c-bcl-2, Cyclin-Dependent Kinase Inhibitor p21, Apoptosis Regulatory Proteins, bcl-2-Associated X Protein
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