ISG12a and its interaction partner NR4A1 are involved in TRAIL-induced apoptosis in hepatoma cells.

In this study, we found that ISG12a was localized in the mitochondria and nucleus and augmented TRAIL-induced apoptosis through intrinsic apoptotic pathway. In addition, ISG12a interacted with NR4A1 and promoted its nuclear-to-cytoplasm translocation. Upon translocate to cytoplasm, NR4A1 targeted mitochondria and induced Bcl2 conformational change, thereby exposing its BH3 domain. Moreover, TRAIL treatment can induce NR4A1 expression through the activation of NF-κB in TRAIL-resistant Huh7 hepatoma cells. Knockdown of NR4A1 could overcome TRAIL resistance. However, in TRAIL-sensitive LH86 liver cancer cells, TRAIL activated the Jun N-terminal kinases signalling pathway. Overall, these results showed that both ISG12a and its interaction partner NR4A1 are involved in TRAIL-mediated apoptosis in hepatoma cells. PMID: 30821058 [PubMed - as supplied by publisher]
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research