Willms, Anna and Schupp, Hella and Poelker, Michelle and Adawy, Alshaimaa and Debus, Jan Frederik and Hartwig, Torsten and Krichel, Tim and Fritsch, Juergen and Singh, Steven and Walczak, Henning and von Karstedt, Silvia and Schaefer, Heiner and Trauzold, Anna (2021) TRAIL-receptor 2-a novel negative regulator of p53. CELL DEATH & DISEASE, 12 (8): 757. ISSN 2041-4889,
Full text not available from this repository. (Request a copy)Abstract
TNF-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2) can induce apoptosis in cancer cells upon crosslinking by TRAIL. However, TRAIL-R2 is highly expressed by many cancers suggesting pro-tumor functions. Indeed, TRAIL/TRAIL-R2 also activate pro-inflammatory pathways enhancing tumor cell invasion, migration, and proliferation. In addition, nuclear TRAIL-R2 (nTRAIL-R2) promotes malignancy by inhibiting miRNA let-7-maturation. Here, we show that TRAIL-R2 interacts with the tumor suppressor protein p53 in the nucleus, assigning a novel pro-tumor function to TRAIL-R2. Knockdown of TRAIL-R2 in p53 wild-type cells increases the half-life of p53 and the expression of its target genes, whereas its re-expression decreases p53 protein levels. Interestingly, TRAIL-R2 also interacts with promyelocytic leukemia protein (PML), a major regulator of p53 stability. PML-nuclear bodies are also the main sites of TRAIL-R2/p53 co-localization. Notably, knockdown or destruction of PML abolishes the TRAIL-R2-mediated regulation of p53 levels. In summary, our finding that nTRAIL-R2 facilitates p53 degradation and thereby negatively regulates p53 target gene expression provides insight into an oncogenic role of TRAIL-R2 in tumorigenesis that particularly manifests in p53 wild-type tumors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PML; PROMOTES; MDM2; EXPRESSION; CELLS; METASTASIS; RESISTANCE; STABILITY; INVASION; ALPHA; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Krankenhaushygiene und Infektiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Sep 2022 06:05 |
| Last Modified: | 20 Sep 2022 06:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47586 |
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