cRel adenovirus

c-Rel is a sequence-specific transcription factor belonging to the NF-κB/Rel family, which also includes RelA (p65), RelB, NF-κB1 (p50/p105), and NF-κB2 (p52/p100). Encoded by the mouse Rel gene (REL gene in humans), c-Rel contains an N-terminal Rel homology domain that mediates DNA binding to κB motifs, dimerization with other NF-κB subunits, and nuclear localization; followed by a C-terminal transcriptional activation domain that drives target gene expression. Its activity is tightly regulated by the classical NF-κB pathway: in resting cells, c-Rel dimers are sequestered in the cytoplasm by IκB proteins; upon pathway activation, IκB proteins are degraded, allowing c-Rel to translocate to the nucleus and regulate transcription. Functionally, c-Rel plays a critical role in immune cell biology, particularly in B cell proliferation, survival, and antibody responses, as well as T cell activation and differentiation (especially Th1 and Th17 polarization). It controls genes involved in cytokine production, co-stimulatory signaling, cell cycle progression, and metabolic adaptation during immune activation. Dysregulation of c-Rel signaling is associated with autoimmune diseases, inflammatory diseases, and lymphoproliferative malignancies; for example, amplification or aberrant activation of the REL gene has been observed in some B-cell lymphomas.

A human adenovirus type 5 vector with E1/E3 deletions, expressing mouse c-Rel under the control of a CMV promoter, provides a versatile tool for gain-of-function studies of NF-κB signaling. The E1 deletion renders the vector replication-incompetent in standard host cells, the E3 deletion increases vector capacity, and the CMV promoter allows for robust, broad, and transient expression in many primary cells and cell lines, including those with low basal c-Rel activity. By increasing c-Rel levels in a controlled, time-limited manner, researchers can investigate how this transcription factor reshapes gene expression, chromatin accessibility, and cellular phenotype. Typical applications include mapping downstream targets through transcriptomic and epigenomic analyses, using reporter genes to detect enhancer-promoter dependence, and dissecting synergistic or antagonistic interactions with other NF-κB subunits or transcriptional cofactors. In immunology, this vector can be used to study thresholds for lymphocyte activation, cytokine secretion, and differentiation trajectories, or to model how c-Rel influences the maturation of antigen-presenting cells and T cell-B cell interactions. In oncology, it supports research into c-Rel-driven survival signaling, stress responses, and therapeutic resistance in models of lymphoid malignancies.