Related Experiment Video

Updated: Aug 13, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex

M Karin1

  • 1Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, CA 92093-0636, USA.

Oncogene
|December 22, 1999
PubMed

Insights

Nuclear factor-kappa B (NF-kappaB) transcription factors are regulated by inhibitor IkappaB proteins. Most NF-kappaB activators trigger IkappaB degradation via phosphorylation and proteasome activity, involving the IkappaB kinase (IKK) complex.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Immunology

Background:

  • Nuclear factor-kappa B (NF-kappaB) is a key transcription factor regulating immune responses and cell survival.
  • NF-kappaB is typically sequestered in the cytoplasm by inhibitor of NF-kappaB (IkappaB) proteins.
  • Activation of NF-kappaB involves the degradation of IkappaB proteins.

Purpose of the Study:

  • To review the identification of proteins within the IkappaB kinase (IKK) complex.
  • To describe the regulatory mechanisms governing IKK activity.
  • To elucidate the physiological functions of the IKK complex.

Main Methods:

  • Literature review of studies on NF-kappaB signaling.
  • Analysis of protein interactions within the IKK complex.
  • Investigation of IKK activation pathways.

Main Results:

  • The IKK complex is a high molecular weight complex crucial for NF-kappaB activation.
  • IKK activation involves phosphorylation-induced degradation of IkappaB.
  • The catalytic core of the IKK complex is a heterodimer of IKKalpha and IKKbeta subunits.

Conclusions:

  • The IKK complex plays a central role in regulating NF-kappaB activity.
  • Understanding IKK regulation is vital for comprehending immune responses and inflammatory processes.
  • Further research into IKK function may reveal therapeutic targets for related diseases.

More Related Videos

Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO13:02

Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO

Published on: December 28, 2019

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells10:57

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells

Published on: January 12, 2020

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...