| MAP3K8 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | MAP3K8 , COT, EST, ESTF, MEKK8, TPL2, Tpl-2, c-COT, AURA2, mitogen-activated protein kinase kinase kinase 8, Tpl2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 191195 MGI: 1346878 HomoloGene: 3812 GeneCards: MAP3K8 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Mitogen-activated protein kinase kinase kinase 8 is an enzyme that in humans is encoded by the MAP3K8 gene. [5] [6] [7]
The gene was identified by its oncogenic transforming activity in cells. The encoded protein is a member of the serine/threonine-specific protein kinase family. This kinase can activate ERK1, ERK2 and p38 MAP kinases. [8] [9] This kinase was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This kinase was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. Studies of a similar gene in rat suggested the direct involvement of this kinase in the proteolysis of NF-kappaB1, p105 (NFKB1). This gene may also start transcription at a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. [7] In mice, the gene is known as TPL2 and is a tumor-suppressor gene whose absence contributes to the development and progression of cancer. [10] However, it functions in other organs as a oncogene, promoting cancer. [11]
MAP3K8 has been shown to interact with AKT1, [12] CHUK, [13] NFKB2, [14] NFKB1, [14] [15] C22orf25 [16] and TNIP2. [17]
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.
Mitogen-activated protein kinase 9 is an enzyme that in humans is encoded by the MAPK9 gene.
RAF kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. The mouse sarcoma virus 3611 contains a RAF kinase-related oncogene that enhances fibrosarcoma induction. RAF is an acronym for Rapidly Accelerated Fibrosarcoma.
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-κB. The human gene for IKBKG is located on the chromosome band Xq28. Multiple transcript variants encoding different isoforms have been found for this gene.
Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, rheumatoid arthritis, cardiovascular and neurodegenerative diseases.
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 gene.
Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the NFKB1 gene.
IκBα 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 nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. In addition, IκBα blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NF-κB's proper functioning.
Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the RELA gene.
Transcription factor RelB is a protein that in humans is encoded by the RELB gene.
The proto-oncogene c-Rel is a protein that in humans is encoded by the REL gene. The c-Rel protein is a member of the NF-κB family of transcription factors and contains a Rel homology domain (RHD) at its N-terminus and two C-terminal transactivation domains. c-Rel is a myeloid checkpoint protein that can be targeted for treating cancer. c-Rel has an important role in B-cell survival and proliferation. The REL gene is amplified or mutated in several human B-cell lymphomas, including diffuse large B-cell lymphoma and Hodgkin's lymphoma.
Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 or MAPK/ERK kinase 6 is an enzyme that in humans is encoded by the MAP2K6 gene, on chromosome 17.
B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene.
Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the MAP3K14 gene.
Dual specificity mitogen-activated protein kinase kinase 7, also known as MAP kinase kinase 7 or MKK7, is an enzyme that in humans is encoded by the MAP2K7 gene. This protein is a member of the mitogen-activated protein kinase kinase family. The MKK7 protein exists as six different isoforms with three possible N-termini and two possible C-termini.
Protein TFG is a protein that in humans is encoded by the TFG gene.
Dual specificity mitogen-activated protein kinase kinase 5 is an enzyme that in humans is encoded by the MAP2K5 gene.
Mitogen-Activated Protein Kinase Kinase Kinase 2 also known as MEKK2 is an enzyme that in humans is encoded by the MAP3K2 gene.
MAP kinase-interacting serine/threonine-protein kinase 2 is an enzyme that in humans is encoded by the MKNK2 gene.
Protein lyl-1 is a protein that in humans is encoded by the LYL1 gene.
