MAP3K8

Function

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. 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. In mice, the gene is known as TPL2 and is a tumor-suppressor gene whose absence contributes to the development and progression of cancer. However, it functions in other organs as a oncogene, promoting cancer.

Interactions

MAP3K8 has been shown to interact with AKT1, CHUK, NFKB2, NFKB1, C22orf25 and TNIP2.

References

References

1. (Aug 1991). "Structure and transforming potential of the human cot oncogene encoding a putative protein kinase". Molecular and Cellular Biology.
2. (May 1993). "Expression cDNA cloning of a serine kinase transforming gene". Oncogene.
3. "Entrez Gene: MAP3K8 mitogen-activated protein kinase kinase kinase 8".
4. (Sep 2013). "Mitogen-activated protein kinases in innate immunity.".
5. (Sep 2016). "TLR and TNF-R1 activation of the MKK3/MKK6-p38α axis in macrophages is mediated by TPL-2 kinase.". Biochemical Journal.
6. DeCicco-Skinner, Kathleen. (2011). "Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis". Oncogene.
7. DeCicco-Skinner, Kathleen. (2011). "Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis". Oncogene.
8. (Aug 2002). "Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription". Molecular and Cellular Biology.
9. (Feb 1999). "The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases". Immunity.
10. (Feb 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology.
11. (Jan 1999). "TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105". Nature.
12. "Molecular Interaction Database".
13. (Jun 2004). "ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability". Molecular and Cellular Biology.