Transforming Stimulated Clone 22 (TSC-22) Interacts Directly with Bromodomain-Containing Protein 7 (BRD7) to Enhance the Inhibition of Extracellular Signal-Regulate Kinase (ERK) Pathway in Ovarian Cancer

Seung-Hoon Lee, D. Choi
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Abstract

Abstract Bromodomain-containing protein 7 (BRD7) participates in many cellular processes and embryo development. BRD7 is down-regulated in various cancers and evidence of its tumor suppressor function has been accumulating. Here, we identified transforming stimulated clone 22 (TSC-22) as a novel BRD7 interacting protein and show its novel function as a positive regulator of BRD7. We found that TSC-22 expression potentiated the inactivation of the extracellular signal-regulate kinase (ERK) pathway by BRD7. Our data establishes TSC-22 as a modulator of BRD7 and unravels the molecular mechanisms that drive the synergistic tumor-suppressing effects of TSC-22 and BRD7. Our findings may open new avenues for developing novel molecular therapies for tumors exhibiting down-regulated BRD7 and/or TSC-22.
转化刺激克隆22(TSC-22)与含溴代胺蛋白7(BRD7)直接相互作用增强对卵巢癌症细胞外信号调节激酶(ERK)通路的抑制作用
含溴结构域蛋白7 (BRD7)参与许多细胞过程和胚胎发育。BRD7在多种癌症中下调,其肿瘤抑制功能的证据越来越多。在这里,我们发现转化刺激克隆22 (TSC-22)是一种新的BRD7相互作用蛋白,并显示其作为BRD7的正调节因子的新功能。我们发现TSC-22的表达增强了BRD7对细胞外信号调节激酶(ERK)通路的失活。我们的数据确定了TSC-22是BRD7的调节剂,并揭示了驱动TSC-22和BRD7协同肿瘤抑制作用的分子机制。我们的发现可能为开发针对BRD7和/或TSC-22下调肿瘤的新型分子疗法开辟了新的途径。
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