In addition to coordinating immune and inflammatory responses, NF- κB/Rel transcription factors control cell survival. Activation of NF- κB antagonizes apoptosis or programmed cell death (PCD) by numerous triggers, including the ligand engagement of “death receptors” such as TNF-Rs and TRAIL-Rs. The anti-apoptotic activity of NF-κB is also crucial to oncogenesis and chemo- and radio-resistance in cancer.

Dr. Franzoso and his laboratory have identified Gadd45β as a pivotal mediator of the protective activity of NF-κB against TNFα. Indeed, in the systems that were examined, Gadd45β appeared to be more relevant to the NF-κB control of apoptosis than previously identified target genes such as Bcl-2 family members, Bcl-XL and A1/Bfl-1, XIAP, and TRAF1/2 and c-IAP1/2. Cytoprotection by Gadd45β involves the inhibition of the c-Jun-N-terminal kinase (JNK) cascade, and this inhibition is central to the control of apoptosis by NF-κB. Dr. Franzoso and others have shown that NF-κB complexes are required to downregulate JNK signaling induced by TNF-R, thus establishing a link between the NF-κB and JNK pathways. Dr. Franzoso’s interest in apoptosis is relevant to research in type I diabetes where apoptosis is a major factor in reduction of β-cell mass.