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NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli
J Svaren1, B R Sevetson, E D Apel
1Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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 12ql3.3-14.1, 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.
Insights
Researchers identified NAB2, a corepressor related to NAB1. NAB2 represses transcription factors NGFI-A and Krox20, and its gene is located on chromosome 12. NAB molecules play a conserved role in evolution.
Area of Science:
- Molecular Biology
- Gene Regulation
- Cancer Biology
Background:
- NAB1 is a known corepressor for transcription factors NGFI-A and Krox20.
- NGFI-A and Krox20 are zinc finger transcription factors encoded by immediate-early genes.
- These transcription factors are involved in cell proliferation and differentiation.
Purpose of the Study:
- To isolate and characterize a novel corepressor, NAB2, related to NAB1.
- To investigate the interaction domains and regulatory mechanisms of NAB2.
- To determine the chromosomal localization of the human NAB2 gene and its potential role in cancer.
Main Methods:
- Isolation and characterization of the NAB2 corepressor.
- Analysis of NAB2 interaction with NGFI-A.
- Expression studies of NAB2 in response to stimuli.
- Chromosomal localization of the human NAB2 gene.
- Comparative genomics analysis with Caenorhabditis elegans.
Main Results:
- NAB2 was identified as a novel corepressor highly related to NAB1.
- NAB2 contains a conserved domain mediating interaction with NGFI-A.
- NAB2 represses the transcriptional activity of both NGFI-A and Krox20.
- NAB2 expression is regulated by serum and nerve growth factor.
- The human NAB2 gene is localized to chromosome 12q13.3-14.1, a region associated with tumors.
- Homologous genes suggest an evolutionarily conserved function for NAB molecules.
Conclusions:
- NAB2 is a functional corepressor that interacts with NGFI-A and Krox20.
- NAB2 plays a role in gene regulation and is implicated in certain cancers due to its chromosomal location.
- The discovery of NAB2 and its homolog in C. elegans highlights the conserved role of NAB proteins in biological processes.