NAB2, A COREPRESSOR OF NGFI-A (EGR-1) AND KROX20, IS INDUCED BY PROLIFERATIVE AND DIFFERENTIATIVE STIMULI

Previous work had identified a corepressor, NAB1, which represses tran scriptional activation mediated by NGFI-A (also known as Egr-1, zif268 , and Krox24) and Krox20. These zinc finger transcription factors are encoded by immediate-early genes and have been implicated in a wide va riety of proliferative and differentiative processes. We have isolated and characterized another corepressor, NAB2, which is highly related to NAB1 within two discrete domains. The first conserved domain of NAB Z mediates an interaction with the R1 domain of NGFI-A. NAB2 represses the activity of both NGFI-A and Krox20, and its expression is regulat ed by some of the same stimuli that induce NGFI-A expression, includin g serum stimulation of fibroblasts and nerve growth factor stimulation of PC12 cells. The human NABZ gene has been localized to chromosome 1 2q13.3-14.1, a region that is rearranged in several solid tumors, lipo mas, uterine leiomyomata, and liposarcomas. Sequencing of the Caenorha bditis elegans genome has identified a gene that bears high homology t o both NAB1 and NAB2, suggesting that NAB molecules fulfill an evoluti onarily conserved role.