Background information
The adenovirus E1A protein both activates and represses gene expression to promote cellular proliferation and inhibit differentiation. CREG (cellular repressor of E1A-stimulated genes) is a cellular protein that antagonizes transcriptional activation and cellular transformation by E1A. CREG was initially isolated in a yeast two-hybrid screen due to its interaction with the TATA-binding protein, TBP. Binding sites for E2F, a key transcriptional reg-ulator of cell cycle progression, are required for repression of the adeno-virus E2 promoter by CREG, and CREG was shown to inhibit activation by E2F. CREG is broadly expressed in adult tissues and is regulated during embryonic development. CREG is a secreted glycoprotein which enhances differentiation of mouse embryonic stem cells and human NTERA-2 cells. CREG activity may contribute to the transcriptional control of cell growth and differentiation.