Severe Liver Degeneration in Mice Lacking the IκB Kinase 2 Gene

@article{Li1999SevereLD,
  title={Severe Liver Degeneration in Mice Lacking the I$\kappa$B Kinase 2 Gene},
  author={Qiutang Li and Daniel J. van Antwerp and Frank Mercurio and Kuo-Fen Lee and Inder M. Verma},
  journal={Science},
  year={1999},
  volume={284},
  pages={321-325}
}
Phosphorylation of inhibitor of kappa B (IκB) proteins is an important step in the activation of the transcription nuclear factor kappa B (NF-κB) and requires two IκB kinases, IKK1 (IKKα) and IKK2 (IKKβ). Mice that are devoid of the IKK2 gene had extensive liver damage from apoptosis and died as embryos, but these mice could be rescued by the inactivation of the gene encoding tumor necrosis factor receptor 1. Mouse embryonic fibroblast cells that were isolated from IKK2–/– embryos showed a… 

Severe liver degeneration and lack of NF-kappaB activation in NEMO/IKKgamma-deficient mice.

In vivo evidence is provided that NEMO/IKKgamma is the first essential, noncatalytic component of the IKK complex, and mutant MEFs show increased sensitivity to TNFalpha-induced apoptosis.

Severe liver degeneration and lack of NF - k B activation in NEMO/IKK g -deficient mice

In vivo evidence is provided that NEMO/IKK g is the first essential, noncatalytic component of the IKK complex, and mutant MEFs show increased sensitivity to TNF a -induced apoptosis.

Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury.

AS602868, a novel chemical inhibitor of IKK2, protected mice from liver injury due to I/R without sensitizing them toward TNF-induced apoptosis and could therefore emerge as a new pharmacological therapy for liver resection, hemorrhagic shock, or transplantation surgery.

I-κB Kinases α and β Have Distinct Roles in Regulating Murine T Cell Function1

It is demonstrated that IKKα and IKKβ have opposite roles on the regulation of anti-CD3-induced apoptosis of double-positive thymocytes, suggesting that IKR and IKR have distinct roles in regulating thymocyte function.

Iκb Kinase α Is Essential for Mature B Cell Development and Function

Results demonstrate that IKKα is critically involved in the prevention of cell death and functional development of mature B cells and transgene expression of bcl-2 could only partially rescue impaired B cell development in IKK α−/− chimeras.

TAB2 Is Essential for Prevention of Apoptosis in Fetal Liver but Not for Interleukin-1 Signaling

It is demonstrated that TAB2 is essential for embryonic development through prevention of liver apoptosis but not for the IL-1 receptor-mediated signaling pathway.

Prevention of hepatic apoptosis and embryonic lethality in RelA/TNFR-1 double knockout mice.

IκB Kinase Signaling Is Essential for Maintenance of Mature B Cells

It is concluded that maintenance of mature B cells depends on IKK-mediated activation of NF-κB, and that B lineage–specific disruption of either IKK signaling by deletion of NEMO, or of IKK2-specific signals by ablation of Ikk2 activity leads to the disappearance of maturity B lymphocytes.

Inactivation of BAD by IKK Inhibits TNFα-Induced Apoptosis Independently of NF-κB Activation

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