Proliferative role of TRAF4 in breast cancer by upregulating PRMT5 nuclear expression
- 503 Downloads
In this study, we examined protein arginine methyltransferase 5 (PRMT5) and tumor necrosis factor receptor-associated 4 (TRAF4) expression in breast cancer to find the interaction mechanism between the two. We examined TRAF4 and PRMT5 expression by immunohistochemistry and found that their expression is positively correlated in breast cancer. Besides, PRMT5 expression was significantly associated with histological type and tumor size (p < 0.05). PRMT5 nuclear expression was significantly associated with HER2 expression (p < 0.05). PRMT5 and TRAF4 were both overexpressed in breast cancer tissues and cells, and we found that PRMT5 binds to the zinc finger structures in TRAF4 by coimmunoprecipitation and Western blotting. We also tested the potential regulatory effect between TRAF4 and PRMT5. TRAF4 upregulated PRMT5 expression, which occurred predominantly in the nucleus, on which TRAF4 promotion of cell proliferation in breast cancer is mainly dependent. PRMT5 may play an important role in activation of the NF-κB signaling pathway.
KeywordsTRAF4 PRMT5 Breast cancer NF-κB Cell proliferation
Tumor necrosis factor receptor-associated factor 4
Protein arginine methyltransferases 5
We thank Dr. Bert W. O’Malley (Baylor College of Medicine) for kindly providing plasmid for Zn fingers domain deletion mutant (Flag-△Zn-TRAF4). This work was supported by a grant from the Educational Commission of Liaoning Province of China (L2014302) and the Doctoral Program of Higher Education, China (20112104110017).
Conflicts of interest
- 24.Harris DP, Bandyopadhyay S, Maxwell TJ, Willard B, DiCorleto PE. Tumor necrosis factor (TNF)-α induction of CXCL10 in endothelial cells requires protein arginine methyltransferase 5 (PRMT5)-mediated nuclear factor (NF)-κB p65 methylation. J Biol Chem. 2014;289(22):15328–39.CrossRefPubMedPubMedCentralGoogle Scholar