ArticleThe Journal of biological chemistry2008
Oligomerization of BAK by p53 utilizes conserved residues of the p53 DNA binding domain.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 92 citations in OpenAlex.
- Mitochondrially Targeted p53-Bad* Fusion Gene Therapy Promotes Apoptosis in Hepatocellular Carcinoma by Pan-Bcl-2 Inhibition.Molecular pharmaceutics · 2025Article
- Epstein-Barr virus replication within differentiated epithelia requires pRb sequestration of activator E2F transcription factors.Journal of virology · 2024Article
- Emerging role and therapeutic implications of p53 in intervertebral disc degeneration.Cell death discovery · 2023Review
- The ARTS of p53-dependent mitochondrial apoptosis.Journal of molecular cell biology · 2023Review
- Elephant TP53-RETROGENE 9 induces transcription-independent apoptosis at the mitochondria.Cell death discovery · 2023Article
- Long noncoding RNA NONMMUT015745 inhibits doxorubicin-mediated cardiomyocyte apoptosis by regulating Rab2A-p53 axis.Cell death discovery · 2022Article
- Prohibitin 1 interacts with p53 in the regulation of mitochondrial dynamics and chemoresistance in gynecologic cancers.Journal of ovarian research · 2022Article
- Review
- Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications.World journal of stem cells · 2021Review
- Targeted Neoadjuvant Therapies in HR+/HER2-Breast Cancers: Challenges for Improving pCR.Cancers · 2021Review
- Making Connections: p53 and the Cathepsin Proteases as Co-Regulators of Cancer and Apoptosis.Cancers · 2020Review
- How the Other Half Lives: What p53 Does When It Is Not Being a Transcription Factor.International journal of molecular sciences · 2019Review
- Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses.The EMBO journal · 2019Article
- Mitochondrially targeted p53 or DBD subdomain is superior to wild type p53 in ovarian cancer cells even with strong dominant negative mutant p53.Journal of ovarian research · 2019Article
- Intracellular displacement of p53 using transactivation domain (p53 TAD) specific nanobodies.mAbs · 2018Article
- Tailoring Chemotherapy for the African-Centric S47 Variant of TP53.Cancer research · 2018Article
- Serine 392 phosphorylation modulates p53 mitochondrial translocation and transcription-independent apoptosis.Cell death and differentiation · 2018Article
- Article
- Investigation on tissue specific effects of pro-apoptotic micro RNAs revealed miR-147b as a potential biomarker in ovarian cancer prognosis.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Genotoxic stress triggers a rapid translocation of p53 to the mitochondria, contributing to apoptosis in a transcription-independent manner. Using immunopurification protocols and mass spectrometry, we previously identified the proapoptotic protein BAK as a mitochondrial p53-binding protein and showed that recombinant p53 directly binds to BAK and can induce its oligomerization, leading to cytochrome c release. In this work we describe a combination of molecular modeling, electrostatic analysis, and site-directed mutagenesis to define contact residues between BAK and p53. Our data indicate that three regions within the core DNA binding domain of p53 make contact with BAK; these are the conserved H2 alpha-helix and the L1 and L3 loop. Notably, point mutations in these regions markedly impair the ability of p53 to oligomerize BAK and to induce transcription-independent cell death. We present a model whereby positively charged residues within the H2 helix and L1 loop of p53 interact with an electronegative domain on the N-terminal alpha-helix of BAK; the latter is known to undergo conformational changes upon BAK activation. We show that mutation of acidic residues in the N-terminal helix impair the ability of BAK to bind to p53. Interestingly, many of the p53 contact residues predicted by our model are also direct DNA contact residues, suggesting that p53 interacts with BAK in a manner analogous to DNA. The combined data point to the H2 helix and L1 and L3 loops of p53 as novel functional domains contributing to transcription-independent apoptosis by this tumor suppressor protein.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.