Willms, Anna, Schupp, Hella, Poelker, Michelle, Adawy, Alshaimaa, Debus, Jan Frederik, Hartwig, Torsten, Krichel, Tim, Fritsch, Juergen, Singh, Steven, Walczak, Henning, von Karstedt, Silvia, Schaefer, Heiner and Trauzold, Anna (2021). TRAIL-receptor 2-a novel negative regulator of p53. Cell Death Dis., 12 (8). LONDON: SPRINGERNATURE. ISSN 2041-4889

Full text not available from this repository.

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: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Willms, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schupp, HellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poelker, MichelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adawy, AlshaimaaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Debus, Jan FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartwig, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krichel, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritsch, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singh, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walczak, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Karstedt, SilviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, HeinerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trauzold, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-590700
DOI: 10.1038/s41419-021-04048-1
Journal or Publication Title: Cell Death Dis.
Volume: 12
Number: 8
Date: 2021
Publisher: SPRINGERNATURE
Place of Publication: LONDON
ISSN: 2041-4889
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PML; PROMOTES; MDM2; EXPRESSION; CELLS; METASTASIS; RESISTANCE; STABILITY; INVASION; ALPHAMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59070

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item