Activation of the IκB Kinase Complex by TRAF6 Requires a Dimeric Ubiquitin-Conjugating Enzyme Complex and a Unique Polyubiquitin Chain

@article{Deng2000ActivationOT,
  title={Activation of the I$\kappa$B Kinase Complex by TRAF6 Requires a Dimeric Ubiquitin-Conjugating Enzyme Complex and a Unique Polyubiquitin Chain},
  author={Li Deng and chen wang and Erika Spencer and Liyong Yang and A. Braun and Jianxin You and Clive Slaughter and Cecile M. Pickart and Zhijian J. Chen},
  journal={Cell},
  year={2000},
  volume={103},
  pages={351-361}
}
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References

SHOWING 1-10 OF 66 REFERENCES
IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation
Activation of the transcription factor nuclear factor kappa B (NF-κB) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IκB. A large multiprotein…
Site-Specific Phosphorylation of IκBα by a Novel Ubiquitination-Dependent Protein Kinase Activity
The ubiquitinproteasome pathway is required for processing the NF-κB1 precursor protein and the activation of NF-κB
Signal-induced ubiquitination of IκBα by the F-box protein Slimb/β-TrCP
Signal-induced phosphorylation of IκBα targets this inhibitor of NF-κB for ubiquitination and subsequent degradation, thus allowing NF-κB to enter the nucleus to turn on its target genes. We report…
Identification and Characterization of an IκB Kinase
The IKK complex: an integrator of all signals that activate NF-κB?
A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways.
Ubiquitin-dependent proteolysis by the proteasome plays an essential role in a number of key biological processes, including cell cycle progression, transcription, and signal transduction (for…
Role of the Ubiquitin—Proteasome Pathway in NF-κB Activation
TLDR
The transcription factor NF-κB (nuclear factor κB) is a heterodimeric protein that plays a pivotal role in immune and inflammatory responses and members of the Rel family of transcriptional activation proteins, but they differ in their modes of synthesis.
Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation.
Noncanonical MMS2-Encoded Ubiquitin-Conjugating Enzyme Functions in Assembly of Novel Polyubiquitin Chains for DNA Repair
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