Research Report 2010 - MDC

Graduate StudentsSeda Cöl ArslanCan Demiroglu*Jan EbertAndrea Oeckinghaus*Kivia A. Pontes de Oliveira*Michael StilmannPhilip Tomann*Technical AssistantsRudolf Dettmer*Sabine JungmannInge KrahnSarah UgowskiSecretariatDaniela Keyner*part of the period reportedFigure 1. Distinct NF-κB dimers are activated by canonical and non-canonical IKK/NF-κB signaling pathways and depend on IKKβ and IKKα,respectively. Both pathways are constitutively activated in Hodgkin lymphoma cells. A nucleus-to-cytoplasm IKK/NF-κB pathway is induced by theDNA damage response and may play a role in therapy resistance of tumor cells. Homeostasis and activity of the IKK complex is regulated by theHsp90-Cdc37 chaperone complex.depends on nuclear shuttling and SUMO-modificationof IKKγ, as well as on the kinase ATM.IKK and NF-κB signal transduction in lymphoidtumor cellsA dysregulation of the IKK/NF-κB system has now beenrecognized as an oncogenic hallmark of an increasingnumber of lymphoma and leukemia entities. We haveinvestigated the origins and the biological functions ofconstitutively activated IKKs and NF-κB and the downstreameffector networks in Hodgkin lymphoma (HL)tumor cells. The IKK/NF-κB system is aberrantly activatedin a cell-autonomous manner, generally involving apersistent activation of the IKK complex, which resultsin constitutive release of NF-κB complexes. In HL cells,both, canonical and non-canonical p100 pathways areactivated (Figure 1). The determination of the global NFκBtarget gene signature in HL cells by microarraysCancer Research 79