Mechanism of aberrant NF-κB activation through the alternative signaling pathway in human lymphomas. Aberrant activation of the alternative pathway. Signaling through CD30, CD40, and LMP1 also activates the alternative NF-κB pathway via NIK and IKKα in HL. These events lead to the phosphorylation and proteolytic processing of the NF-κB2 precursor protein p100 as well as the translocation of mature p52/RelB dimers into the nucleus. In ATL, TAX can bind to p100 in the cytoplasm and increase its proteolytic processing. Mutations of NF-κB2/p100, leading to a decreased inhibitory p100 function and an increased p52 activity, have been found in cases of ABC-DLBCL. Illustration by Kenneth Probst.