FTH1 binds to Daxx and inhibits Daxx-mediated cell apoptosis

Abstract

As a highly conserved nuclear protein, death domain-associated protein (Daxx) plays an important role in transcriptional control, carcinogenesis, and resistance to virus infection and so on. In order to further investigate the mechanism of Daxx, the yeast two-hybrid technique was used to screen the intra-cellular proteins interacting with Daxx. And 13 positive colonies and three proteins interacting with Daxx were obtained. One of the candidate proteins was identified as ferritin, heavy polypeptide 1(FTH1). The interaction between Daxx and FTH1 was further supported by GST pull-down and co-immunoprecipitation respectively. Then Daxx was determined to induce apoptosis and FTH1 can inhibit Daxx-mediated apoptosis. Besides, it is found that Daxx mediated apoptosis through the Fas-Daxx-ASK1-JNK1 signaling pathway, while FTH1 can inhibit the activation of JNK signaling pathway. We present evidence to demonstrate the FTH1 and Daxx are able to participate in apoptosis pathway through JNK signal molecule and FTH1 can inhibit this pathway.

Ferritin Heavy Chain in Triple Negative Breast Cancer: A Favorable Prognostic Marker that Relates to a Cluster of Differentiation 8 Positive (CD8+) Effector T-cell Response

“…8 C ). In addition, nFTH1 has been shown to interact with death domain-associated protein (DAXX) and inhibit DAXX-mediated apoptosis (16). Interestingly, a time-dependent cytoplasm-to-nucleus switching of FTH1 has been observed in HEK-293 cell lines through activation of the CXCL12-CXCR4 signaling pathway (48).…”

“…The ferritin complex captures intracellular ferrous iron (Fe 2+ ) and converts it into ferric iron (Fe 3+ ) by the ferroxidase activity of FTH1, which potentially reduces DNA damage caused by Fe 2+ induced reactive oxygen species (ROS) and protects cancer cells from cell death (12, 13). FTH1 interacts with some important pathways related to TNBC, such as the NK-κB pathway (14, 15) and apoptosis pathways (16), which indicates the importance of this protein in TNBC progression. Also, FTH1 has been suggested as an immunomodulatory protein in various other cancer types including melanoma (17) and non-TNBC (18).…”

Germinal center kinases in immune regulation

“…44,45 In addition, Ferritin heavy chain (FTH1) may bind directly with Daxx to regulate apoptosis. 46 At this point, it remains unknown how Daxx mechanistically regulates the activity and cellular localization of MST1 and how MST1 and Daxx may interplay with Rassf1 and FTH1. MST1 activity may be influenced by the oxidative environment changes in inflammatory sites.…”

Advances in the study of the biological function of Daxx

“…In order to further investigate the mechanism of Daxx, yeast two-hybrid technique was used to screen the intracellular proteins interacting with Daxx (Liu et al, 2012), and 13 positive colonies and three proteins interacting with Daxx were obtained. One of the candidate proteins was identified as ferritin, heavy polypeptide 1 (FTH1).…”