LUBAC and its enzymatic activities in the development and therapy of ABC-diffuse large B-cell lymphoma

It is currently unknown how the two different LUBAC-contained ubiquitin E3s, possibly differentially, affect DLBCL development and therapy and, most importantly, what the specific roles of linear ubiquitination in the pathogenesis of this disease are and how they may differ from those of the cIAPs. We plan to delineate the tumor biology of LUBAC in ABC-DLBCL (aim 1), study the impact of LUBAC’s enzymatic activities, as compared to those of cIAP1/2, on composition and functional signaling outputs of the CBM and the My-T-BCR complexes in ABC-DLBCL cells (aim 2), and determine how HOIP inhibition impacts therapies targeting other therapeutic vulnerabilities of ABC-DLBCL (aim 3).