TNFa converting enzyme

Human TNFa is a protein that exists in both soluble (157amino acids) and transmem-brane form (233 amino acids). Soluble TNFa is released from the cell membrane through a TNF-converting enzyme and exists as a ho-motrimer in aqueous solution (556,557). It is produced primarily by monocytes/macro-phages in response to various inflammatory stimuli, but can also be produced by other cell types, including T-cells, NK cells, dendritic cells, and endothelial cells. 

Another approach is the inhibition of the TNF-converting enzyme (TACE), which converts proTNF into its mature, proinflammatory form. Also, numerous inhibitors of P38 and Erk-MAP kinases have been synthesized and some have reached the clinical trial stage. MAP-p38 kinase occupies a central role in the signaling network responsible for the up-regulation of proinflammatory cytokines like interleukin 1 and TNFa. The pathway of Erk-MAP kinase is often up-regulated in human tumors and as such represents an attractive target for the development of anticancer drugs. ... 

NEMO kinase (regulatory subunit IKKy), NFkB (nuclear factor kappa B lymphoma) essential modulator, inhibitor of kappa kinase gamma (IKKy). Protein kinase C-interacting protein p62/sequestosome-l, is activated by interleukin IL-IP in sequence, it activates of nuclear factor NFkB in TNFa-stimulated cells (Zotti T et al Mol Immunol 2014 58 27-31). NEMO promotes vFFlP (Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein) expression by Kaposi sarcoma associated herpesvirus (KSHV) (Tolani B et al J Virol 2014 March 26 PMID 24672029). 

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