Proposed model describing how loss of Tpl2 results in increased inflammation and tumorigenesis.

<p>Tpl2 is normally held in complex with p105 NF-κB, preventing proteolysis and activation of the NF-κB and MAPK signaling pathways. Without Tpl2, NF-κB activity increases (see reference 19), resulting in increased production of NF-κB target genes such as COX-2. COX-2 activation results in the conversion of arachidonic acid to PGE₂, which then can bind to one of four G-protein linked receptors (EP1–EP4). EP2 and EP4 receptor activation causes the formation of cAMP from ATP. cAMP can then bind to cAMP response genes such as CREB and PKA. The end result is an increase in inflammatory and cell survival proteins, ultimately contributing to both tumorigenesis and inflammation.