The present invention concerns methods and reagents useful in modulating transcription factor gene expression in a variety of applications, including methods of use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siRNA), short interfering RNA (siRNA), and doublestranded RNA (dsRNA) molecules capable of mediating RNA interference (RNAi) against E2F1, NFkB, CREB-1, and/or CDC2A gene expression, useful in the treatment of cell cycle disorders, inflammatory conditions, reproductive disorders, cancers and any other condition that responds to modulation of E2F1, NFkB, CREB-1, and/or CDC2A expression and/or activity.