IKK2
Encyclopedia
IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a protein
that in humans is encoded by the IKBKB (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta) gene
.
that serves as a protein
subunit of IκB kinase
, which is a component of the cytokine
-activated intracellular signaling pathway involved in triggering immune responses
. Its activity causes activation of a transcription factor
known as Nuclear Transcription factor kappa-B or NF-κB. Activated IKK-β phosphorylates
a protein called the inhibitor
of NF-κB, IκB (IκBα), which binds NF-κB to inhibit its function. Phosphorylated IκB is degraded
via the ubiquitin
ation pathway, freeing NF-κB, and allowing its entry into the nucleus
of the cell where it activates various genes involved in inflammation
and other immune responses.
cells
following a stroke
. citation needed, Oct 2011. If NF-κB inhibition by IKK-β is blocked, damaged cells within the brain stay alive, and according to a study performed by the University of Heidelberg and the University of Ulm, the cells even appear to make some recovery. The size of the infarct, or tissue killed or damaged by ischemia
, is reduced in mice in which IKK-β has been blocked. Additionally, experimental mice with an overactive form of IKK-β experience loss of many more neurons than normal mice after a stroke-simulating event. Researchers found a molecule that could block the signaling of IKK-β for up to four and a half hours. In another study, researchers found that inhibiting IKK-β prevented kidney and wasting diseases in an animal model
used to study wasting diseases of human AIDS
sufferers.
with
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the IKBKB (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta) gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
IKK-β is an enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that serves as a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
subunit of IκB kinase
IκB kinase
The IκB kinase is an enzyme complex that is involved in propagating the cellular response to inflammation.The IκB kinase enzyme complex is part of the upstream NF-κB signal transduction cascade...
, which is a component of the cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
-activated intracellular signaling pathway involved in triggering immune responses
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. Its activity causes activation of a transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
known as Nuclear Transcription factor kappa-B or NF-κB. Activated IKK-β phosphorylates
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
a protein called the inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of NF-κB, IκB (IκBα), which binds NF-κB to inhibit its function. Phosphorylated IκB is degraded
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
via the ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
ation pathway, freeing NF-κB, and allowing its entry into the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
of the cell where it activates various genes involved in inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and other immune responses.
Clinical significance
IKK-β plays a significant role in brainBrain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
following a stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
. citation needed, Oct 2011. If NF-κB inhibition by IKK-β is blocked, damaged cells within the brain stay alive, and according to a study performed by the University of Heidelberg and the University of Ulm, the cells even appear to make some recovery. The size of the infarct, or tissue killed or damaged by ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, is reduced in mice in which IKK-β has been blocked. Additionally, experimental mice with an overactive form of IKK-β experience loss of many more neurons than normal mice after a stroke-simulating event. Researchers found a molecule that could block the signaling of IKK-β for up to four and a half hours. In another study, researchers found that inhibiting IKK-β prevented kidney and wasting diseases in an animal model
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...
used to study wasting diseases of human AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
sufferers.
Interactions
IKK-β (IKBKB) has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with
- CDC37CDC37Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the CDC37 gene.The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae. This protein is a molecular chaperone with specific function in cell signal transduction...
, - CHUKCHUKInhibitor of nuclear factor kappa-B kinase subunit alpha also known as IKK1 or conserved helix-loop-helix ubiquitous kinase is a protein kinase that in humans is encoded by the CHUK gene. IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription...
- CTNNB1Beta-cateninBeta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...
, - FANCAFANCAFanconi anemia, complementation group A, also known as FANCA, is a protein which in humans is encoded by the FANCA gene.- Function :...
, - IKBKGIKBKGNF-kappa-B essential modulator also known as inhibitor of nuclear factor kappa-B kinase subunit gamma is a protein that in humans is encoded by the IKBKG gene. NEMO is a subunit of the IκB kinase that activates NF-κB. The human gene for IKBKG is located on chromosome Xq28...
- IRAK1IRAK1Interleukin-1 receptor-associated kinase 1 is an enzyme that in humans is encoded by the IRAK1 gene.-Interactions:IRAK1 has been shown to interact with Myd88, IKBKG, IKK2, TRAF6, CHUK and Ubiquitin C.-Further reading:...
, - NFKBIA,
- MAP3K14MAP3K14Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase is an enzyme that in humans is encoded by the MAP3K14 gene.- Function :...
, - NFKB1NFKB1Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the NFKB1 gene.This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and...
, - NFKBIBNFKBIBNF-kappa-B inhibitor beta is a protein that in humans is encoded by the NFKBIB gene.-Interactions:NFKBIB has been shown to interact with RELA, Retinoid X receptor alpha and IKK2.-Further reading:...
, - NCOA3Nuclear receptor coactivator 3The nuclear receptor coactivator 3 also known as NCOA3 is a protein that, in humans, is encoded by the NCOA3 gene. NCOA3 is also frequently called 'amplified in breast 1' , steroid receptor coactivator-3 , or thyroid hormone receptor activator molecule 1 .-Function:NCOA3 is a transcriptional...
, - PPM1BPPM1BProtein phosphatase 1B is an enzyme that in humans is encoded by the PPM1B gene.-Interactions:PPM1B has been shown to interact with IKBKG, IKK2, Cyclin-dependent kinase 2, Cyclin-dependent kinase 6, CHUK and MAP3K7.-Further reading:...
, - TNFRSF1ATNFRSF1ATumor necrosis factor receptor superfamily member 1A is a protein that in humans is encoded by the TNFRSF1A gene. The protein encoded by this gene is a member of the Tumor necrosis factor receptor superfamily, which also contains TNFRSF1B. This protein is one of the major receptors for the tumor...
, and - TRAF2TRAF2TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.-Interactions:TRAF2 has been shown to interact with BCL10, CD30, CFLAR, IKK2, MAP3K7IP2, CD137, Caveolin 1, CD27, TNFRSF13B, TANK-binding kinase 1, TRAF1, CD40, UBE2N, MAP3K14, MAP4K2, CASP8AP2, HIVEP3,...
.
See also
- IκB kinaseIκB kinaseThe IκB kinase is an enzyme complex that is involved in propagating the cellular response to inflammation.The IκB kinase enzyme complex is part of the upstream NF-κB signal transduction cascade...