ArticleOncogenesis2013
Tumor suppressor protein Pdcd4 interacts with Daxx and modulates the stability of Daxx and the Hipk2-dependent phosphorylation of p53 at serine 46.
Article in Oncogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- PDCD4: A Double-Edged Sword in Neurological Diseases.Molecular neurobiology · 2026Review
- The crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cells.Cell death discovery · 2025Article
- Microglial Pdcd4 deficiency mitigates neuroinflammation-associated depression via facilitating Daxx mediated PPARγ/IL-10 signaling.Journal of neuroinflammation · 2024Article
- Tumor Suppressor p53 Down-Regulates Programmed Cell Death Protein 4 (PDCD4) Expression.Current oncology (Toronto, Ont.) · 2023Article
- Gene deficiency or pharmacological inhibition of PDCD4-mediated FGR signaling protects against acute kidney injury.Acta pharmaceutica Sinica. B · 2021Article
- DAXX mediates high phosphate-induced endothelial cell apoptosis in vitro through activating ERK signaling.PeerJ · 2020Article
- DAXX in cancer: phenomena, processes, mechanisms and regulation.Nucleic acids research · 2019Review
- Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions.International journal of molecular sciences · 2019Review
- Interrelation of the Circulating and Tissue MicroRNA-21 with Tissue PDCD4 Expression and the Invasiveness of Iraqi Female Breast Tumors.Indian journal of clinical biochemistry : IJCB · 2019Article
- Cbl-b deficiency provides protection against UVB-induced skin damage by modulating inflammatory gene signature.Cell death & disease · 2018Article
- PDCD4 Knockdown Induces Senescence in Hepatoma Cells by Up-Regulating the p21 Expression.Frontiers in oncology · 2018Article
- Role of programmed cell death 4 in diseases: a double-edged sword.Cellular & molecular immunology · 2017Article
- Daxx inhibits hypoxia-induced lung cancer cell metastasis by suppressing the HIF-1α/HDAC1/Slug axis.Nature communications · 2016Article
- CRL3IBTK Regulates the Tumor Suppressor Pdcd4 through Ubiquitylation Coupled to Proteasomal Degradation.The Journal of biological chemistry · 2015Article
- Article
- Role of HIPK2 in kidney fibrosis.Kidney international supplements · 2014Review
- Verbascoside promotes apoptosis by regulating HIPK2-p53 signaling in human colorectal cancer.BMC cancer · 2014Article
- Enhanced arginine methylation of programmed cell death 4 protein during nutrient deprivation promotes tumor cell viability.The Journal of biological chemistry · 2014Article
- An evolutionarily conserved interaction of tumor suppressor protein Pdcd4 with the poly(A)-binding protein contributes to translation suppression by Pdcd4.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor protein Pdcd4 is a nuclear/cytoplasmic shuttling protein that has been implicated in the development of several types of human cancer. In the nucleus, Pdcd4 affects the transcription of specific genes by modulating the activity of several transcription factors. We have identified the Daxx protein as a novel interaction partner of Pdcd4. Daxx is a scaffold protein with roles in diverse processes, including transcriptional regulation, DNA-damage signaling, apoptosis and chromatin remodeling. We show that the interaction of both proteins is mediated by the N-terminal domain of Pdcd4 and the central part of Daxx, and that binding to Pdcd4 stimulates the degradation of Daxx, presumably by disrupting the interaction of Daxx with the de-ubiquitinylating enzyme Hausp. Daxx has previously been shown to serve as a scaffold for protein kinase Hipk2 and tumor suppressor protein p53 and to stimulate the phosphorylation of p53 at serine 46 (Ser-46) in response to genotoxic stress. We show that Pdcd4 also disrupts the Daxx-Hipk2 interaction and inhibits the phosphorylation of p53. We also show that ultraviolet irradiation decreases the expression of Pdcd4. Taken together, our results support a model in which Pdcd4 serves to suppress the phosphorylation of p53 in the absence of DNA damage, while the suppressive effect of Pdcd4 is abrogated after DNA damage owing to the decrease of Pdcd4. Overall, our data demonstrate that Pdcd4 is a novel modulator of Daxx function and provide evidence for a role of Pdcd4 in restraining p53 activity in unstressed cells.
Identifiers
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Registered trials
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.