NAB2, a Corepressor of NGFI-A (Egr-1) and Krox20, Is Induced by Proliferative and Differentiative Stimuli

Abstract

Previous work had identified a corepressor, NAB1, which represses transcriptional 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 variety 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 NAB2 mediates an interaction with the R1 domain of NGFI-A. NAB2 represses the activity of both NGFI-A and Krox20, and its expression is regulated by some of the same stimuli that induce NGFI-A expression, including serum stimulation of fibroblasts and nerve growth factor stimulation of PC12 cells. The human NAB2 gene has been localized to chromosome 12q13.3-14.1, a region that is rearranged in several solid tumors, lipomas, uterine leiomyomata, and liposarcomas. Sequencing of the Caenorhabditis elegans genome has identified a gene that bears high homology to both NAB1 and NAB2, suggesting that NAB molecules fulfill an evolutionarily conserved role.Transcriptional control plays a vital role in regulating fundamental cellular processes such as proliferation, differentiation, and cell death. Changes in gene expression are often effected by altering the expression level, activity, and/or nuclear localization of transcription factors that bind to promoter and enhancer regions. In addition, many transcription factors are regulated by direct interactions with other proteins which modulate the level of transcriptional activation.

HGF induces fibronectin matrix synthesis in melanoma cells through MAP kinase-dependent signaling pathway and induction of Egr-1

“…To assess the contribution of the Egr-1 transcription factor to fibronectin expression, MeWo cells were infected with recombinant adenovirus to overexpress NAB2 (AdNAB2). NAB2 is a corepressor molecule that directly binds Egr-1 and inhibits its transactivating potential (Svaren et al, 1996). As expected, overexpression of NAB2 had no effect on Egr-1 protein induction mediated by HGF (Figure 6b).…”

Sequential Expression of Egr‐1 and Egr‐3 in Hippocampal Granule Cells Following Electroconvulsive Stimulation

“…These studies reveal a switch over time in the dominant Egr family member interacting with the Egr response element. In this context, it is noteworthy that Egr-] and Egr-3 are differentially sensitive to suppression by NAB 1 and NAB2, recently identified proteins that suppress Egr-l-, but not Egr-3-, mediated transcription (Russo and Milbrandt, 1995;Svaren et al, 1996). Accordingly, swapping of Egr-I for Egr-3 could have a major impact on Egr-mediated transcription as it would render it insensitive to suppression by NAB family members.…”

Multiple promoter elements differentially regulate the expression of the mouse tenascin gene

“…Phosphorylation might be responsible for the difference in the size between the Krox24 complexes that we observed in binding experiments. Alternatively, since Krox24 contains an inhibitory domain of 34 amino acids termed R1 (30) that has been shown to interact with several corepressors (31,32), the larger size of complex 1, which is correlated with the repressor function of Krox24, may represent a ternary complex that includes a corepressor.…”