Abstract
The activation of NF-κB by receptors in the tumor necrosis factor (TNF) receptor and Toll/interleukin-1 (IL-1) receptor families requires the TRAF family of adaptor proteins. Receptor oligomerization causes the recruitment of TRAFs to the receptor complex, followed by the activation of a kinase cascade that results in the phosphorylation of IκB. TANK is a TRAF-binding protein that can inhibit the binding of TRAFs to receptor tails and can also inhibit NF-κB activation by these receptors. However, TANK also displays the ability to stimulate TRAF-mediated NF-κB activation. In this report, we investigate the mechanism of the stimulatory activity of TANK. We find that TANK interacts with TBK1 (TANK-binding kinase 1), a novel IKK-related kinase that can activate NF-κB in a kinase-dependent manner. TBK1, TANK and TRAF2 can form a ternary complex, and complex formation appears to be required for TBK1 activity. Kinase-inactive TBK1 inhibits TANK-mediated NF-κB activation but does not block the activation mediated by TNF-α, IL-1 or CD40. The TBK1-TANK-TRAF2 signaling complex functions upstream of NIK and the IKK complex and represents an alternative to the receptor signaling complex for TRAF-mediated activation of NF-κB.
Original language | English (US) |
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Pages (from-to) | 6694-6704 |
Number of pages | 11 |
Journal | EMBO Journal |
Volume | 18 |
Issue number | 23 |
State | Published - Dec 1 1999 |
Externally published | Yes |
Keywords
- IKK
- NF-κB
- TANK
- TBK1
- TRAF2
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology