Skip to Content
Merck
  • UBE2O negatively regulates TRAF6-mediated NF-κB activation by inhibiting TRAF6 polyubiquitination.

UBE2O negatively regulates TRAF6-mediated NF-κB activation by inhibiting TRAF6 polyubiquitination.

Cell research (2013-02-06)
Xiaofei Zhang, Juan Zhang, Long Zhang, Hans van Dam, Peter ten Dijke
ABSTRACT

Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is a key regulator of the activation of transcription factor NF-κB by the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily. Recruitment of TRAF6 to the receptor-associated IRAK1-IRAK4-MyD88 adaptor protein complex induces lysine 63 (K63) autopolyubiquitination of TRAF6, which leads to further recruitment of downstream regulators, such as TAB2/3 and TAK1, and subsequently triggers NF-κB activation. Here, we identified the putative E2 ubiquitin-conjugating (UBC) enzyme UBE2O as a novel negative regulator of TRAF6-dependent NF-κB signaling. We found that UBE2O binds to TRAF6 to inhibit its K63-polyubiquitination, and to prevent the activation of NF-κB by IL-1β and lipopolysaccharides (LPS). We further show that the inhibitory effect of UBE2O is independent of its carboxy-terminal UBC domain. In contrast, we found that UBE2O acts to disrupt the IL-1β-induced association of TRAF6 with MyD88. These results provide novel insight into the regulation of signaling by IL-1R/TLR and TRAF6.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid
Millipore
Anti-c-Myc Agarose Affinity Gel antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)