Cancers, Vol. 11, Pages 1167: TRAIL Induces Nuclear Translocation and Chromatin Localization of TRAIL Death Receptors

Cancers, Vol. 11, Pages 1167: TRAIL Induces Nuclear Translocation and Chromatin Localization of TRAIL Death Receptors Cancers doi: 10.3390/cancers11081167 Authors: Ufuk Mert Alshaimaa Adawy Elisabeth Scharff Pierre Teichmann Anna Willms Verena Haselmann Cynthia Colmorgen Johannes Lemke Silvia von Karstedt Jürgen Fritsch Anna Trauzold Binding of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to the plasma membrane TRAIL-R1/-R2 selectively kills tumor cells. This discovery led to evaluation of TRAIL-R1/-R2 as targets for anti-cancer therapy, yet the corresponding clinical trials were disappointing. Meanwhile, it emerged that many cancer cells are TRAIL-resistant and that TRAIL-R1/-R2-triggering may lead to tumor-promoting effects. Intriguingly, recent studies uncovered specific functions of long ignored intracellular TRAIL-R1/-R2, with tumor-promoting functions of nuclear (n)TRAIL-R2 as the regulator of let-7-maturation. As nuclear trafficking of TRAIL-Rs is not well understood, we addressed this issue in our present study. Cell surface biotinylation and tracking of biotinylated proteins in intracellular compartments revealed that nTRAIL-Rs originate from the plasma membrane. Nuclear TRAIL-Rs-trafficking is a fast process, requiring clathrin-dependent endocytosis and it is TRAIL-dependent. Immunoprecipitation and immunofluorescence approaches revealed an interaction of nTRAIL-R2 with the nucleo-cytoplasmic shuttle protein Exportin-1...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research