Innate immunity-induced IRF3 signaling suppress TGF-β via Smad


Transforming growth factor β (TGF-β) signaling is a central regulator of many process, including immune responses and cancer progression. By investigating the innate host defense, Xu et al. found RIG-I-Like receptor (RLR) signaling suppress TGF-β via activation of Interferon regulatory factor 3 (IRF3). The article was published on Molecular Cell, recently.


Most of the cells perform non-specific innate host defense to quickly recognize pathogens and start a series of defensive activities. RLRs can bind to viral double-stranded RNA (dsRNA) and indirectly activate the signaling mediator IRF3. Researchers found IRF3 suppress TGF-β responses in two ways: 1) by competing with TGF-β on binding to Smad3, IRF3 inhibit TGF-β signaling that transfer through Smad3 in the cell plasma; 2) interfere the interaction between functional Smad3 transcription complexes and the coregulators in the nucleus. The findings indicate a crosstalk between IRF3 mediated innate defense and Smad mediated TGF-β signaling. The repression of TGF-β was proved to inhibit epithelial-mesenchymal transition (EMT) and differentiation of Treg cells, in addition, may potently affect cancer development and progression as well as the modulation of immune responses.


Mol Cell. 2014 Dec 18;56(6):723-37.

Related Products

Cat.No. Product Name Information Publications Customer Product Validation
S1067 SB431542 SB431542 is a potent and selective inhibitor of ALK5 with IC50 of 94 nM in a cell-free assay, 100-fold more selective for ALK5 than p38 MAPK and other kinases. (452) (11)
S1274 BX-795 BX-795 is a potent and specific PDK1 inhibitor with IC50 of 6 nM, 140- and 1600-fold more selective for PDK1 than PKA and PKC in cell-free assays, respectively. Meanwhile, in comparison to GSK3β more than 100-fold selectivity observed for PDK1. BX-795 modulates autophagy via inhibiting ULK1. (51) (4)

Related Targets