RT Journal Article
SR Electronic
T1 Trim13 potentiates TLR2-mediated NF-κB activation via K29-linked polyubiquitination of TRAF6
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.116.106716
DO 10.1124/mol.116.106716
A1 Bin Huang
A1 Suk-Hwan Baek
YR 2017
UL http://molpharm.aspetjournals.org/content/early/2017/01/13/mol.116.106716.abstract
AB Ubiquitination is a versatile post-translational modification involved in NF-κB activation of TLR signaling. Here, we demonstrated that Trim13, an E3 ubiquitin ligase, is up-regulated in macrophages upon stimulation with TLR2 ligand. Knock-down of Trim13 attenuated TLR2-mediated production of cytokines/chemokines and formation of foam cells, as well as activation of NF-κB. Trim13 interacts with TRAF6 and potentiates NF-κB activity via ubiquitination of TRAF6. Overexpression of inactive mutant (C10/13A) or RING deletion mutant of Trim13 did not potentiate ubiquitination of TRAF6 or activation of NF-κB. These results suggest that the effects of Trim13 are dependent on its E3 ligase activity. Trim13 used K29-linked polyubiquitin chains for TRAF6 ubiquitination to promote NF-κB activity and thus potentiated activation of TLR2-mediated immune responses. Our data identify Trim13 as a positive regulator of NF-κB activation and indicate that K29-linked polyubiquitination is a specific ubiquitin-linked pattern involved in the control of TLR2 signaling.