IKK-β also known as inhibitor of nuclear factor kappa-B kinase subunit beta is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''IKBKB'' (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta)

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

IKK-β is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that serves as a

subunit of

IκB kinase The IκB kinase (IkappaB kinase or IKK) is an enzyme complex that is involved in propagating the cellular response to inflammation, specifically the regulation of lymphocytes. The IκB kinase enzyme complex is part of the upstream NF-κB signal ...

, which is a component of the

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

-activated

intracellular signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

pathway involved in triggering immune responses. IKK's activity causes activation of a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

known as Nuclear Transcription factor kappa-B or

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found i ...

. Activated IKK-β

phosphorylates In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

a protein called the ''

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

of NF-κB'', IκB (

IκBα IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; NFKBIA) is one member of a family of cellular proteins that function to inhibit the NF-κB transcription factor. IκBα inhibits NF-κB by masking the nuc ...

), which binds NF-κB to inhibit its function. Phosphorylated IκB is degraded via the

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...

ation pathway, freeing NF-κB, and allowing its entry into the

nucleus Nucleus (: nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucleu ...

of the cell where it activates various genes involved in

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

and other immune responses.

Clinical significance

IKK-β plays a significant role in

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

cells following a

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

. If

activation by IKK-β is blocked, damaged cells within the brain stay alive, and according to a study performed by the

University of Heidelberg Heidelberg University, officially the Ruprecht Karl University of Heidelberg (; ), is a public university, public research university in Heidelberg, Baden-Württemberg, Germany. Founded in 1386 on instruction of Pope Urban VI, Heidelberg is List ...

and the University of Ulm, the cells even appear to make some recovery. Inhibition of IKK and IKK-related kinases has been investigated as a therapeutic option for the treatment of inflammatory diseases and cancer. The small-molecule inhibitor of IKK2 SAR113945, developed by Sanofi-Aventis, was evaluated in patients with knee osteoarthritis.

Interactions

IKK-β (IKBKB) has been shown to interact with *

HDAC9 Histone deacetylase 9 is an enzyme that in humans is encoded by the ''HDAC9'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alter ...

, *

CDC37 Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the ''CDC37'' gene. This protein is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae. This protein is a HSP90 Co-chaperone with spec ...

, *

CHUK Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-α) also known as IKK1 or conserved helix-loop-helix ubiquitous kinase (CHUK) is a protein kinase that in humans is encoded by the ''CHUK'' gene. IKK-α is part of the IκB kinase c ...

CTNNB1 Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcr ...

, *

FANCA Fanconi anaemia, complementation group A, also known as FAA, FACA and FANCA, is a protein which in humans is encoded by the ''FANCA'' gene. It belongs to the Fanconi anaemia complementation group (FANC) family of genes of which 12 complementatio ...

, *

IKBKG NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the ''IKBKG'' gene. NEMO is a subunit of the IκB kinase complex that activates NF-� ...

IRAK1 Interleukin-1 receptor-associated kinase 1 (IRAK-1) is an enzyme in humans encoded by the ''IRAK1'' gene. IRAK-1 plays an important role in the regulation of the expression of inflammatory genes by immune cells, such as monocytes and macrophages, ...

, * NFKBIA, *

MAP3K14 Mitogen-activated protein kinase kinase kinase 14 (MAP3K14), also known as NF-kappa-B-inducing kinase (NIK), is a MAP kinase kinase kinase enzyme that in humans is encoded by the ''MAP3K14'' gene. Function This gene encodes mitogen-activated p ...

, *

NFKB1 Nuclear 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 pro ...

, * NFKBIB, * NCOA3, * PPM1B, *

TNFRSF1A Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFα). Function The protein encoded ...

, and *

TRAF2 TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, a ...

Function

Clinical significance

Interactions

References

See also