NFkB Pathway

NFkB1 and NFkB2 are members of the Rel/NFkB family of transcription factors that also includes RelA, c-Rel, and RelB. Rel/NFkB members regulate the expression of genes that participate in immune, apoptotic and oncogenic processes. NFkB is predominantly localized in the cytoplasm as a complex with inhibitory IkB proteins and is released and translocated to the nucleus after phosphorylation of IkB. Both NFkB1 (105 kDa) and NFkB2 (100 kDa) are synthesized as precursor molecules that are proteolytically cleaved to 50 and 52 kDa active subunits. NFkB appears to have contradictory functions in apoptosis and cell survival. NFkB mediates the survival response of many signals by inhibiting p53-dependent apoptosis and up-regulating anti-apoptotic members of the Bcl-2 family, and caspase inhibitors such as XIAP, and FLIP. In contrast, NFkB is also activated by apoptotic stimuli involved in DNA damage and mediates upregulation of pro-apoptotic genes such as TRAIL R2/DR5, Fas, and Fas ligand.