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NAB2是神经生长因子诱导蛋白A(Egr-1)和Krox20的一种共抑制因子,由增殖和分化刺激所诱导。

NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli.

作者信息

Svaren J, Sevetson B R, Apel E D, Zimonjic D B, Popescu N C, Milbrandt J

机构信息

Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

出版信息

Mol Cell Biol. 1996 Jul;16(7):3545-53. doi: 10.1128/MCB.16.7.3545.

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.

摘要

先前的研究已经鉴定出一种共抑制因子NAB1,它能抑制由NGFI-A(也称为Egr-1、zif268和Krox24)和Krox20介导的转录激活。这些锌指转录因子由即早基因编码,并参与了多种增殖和分化过程。我们已经分离并鉴定了另一种共抑制因子NAB2,它在两个离散结构域内与NAB1高度相关。NAB2的第一个保守结构域介导与NGFI-A的R1结构域的相互作用。NAB2抑制NGFI-A和Krox20的活性,其表达受一些诱导NGFI-A表达的相同刺激调控,包括成纤维细胞的血清刺激和PC12细胞的神经生长因子刺激。人类NAB2基因已定位到染色体12q13.3-14.1,该区域在几种实体瘤、脂肪瘤、子宫平滑肌瘤和脂肪肉瘤中发生重排。秀丽隐杆线虫基因组测序鉴定出一个与NAB1和NAB2都具有高度同源性的基因,这表明NAB分子发挥着进化上保守的作用。

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