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首页> 外文期刊>Journal of proteome research >Proteomic Analysis of a PDEF Ets Transcription Factor-interacting Protein Complex
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Proteomic Analysis of a PDEF Ets Transcription Factor-interacting Protein Complex

机译：PDEF Ets转录因子相互作用蛋白复合物的蛋白质组学分析。

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摘要

Ets proteins are a family of transcription factors that share an 85 amino acid conserved DNA binding domain, the ETS domain. The 27 known human Ets transcription factors control multiple biological processes, including cellular proliferation, differentiation, apoptosis, angiogenesis, transformation, and invasion. Overexpression of some Ets genes has been linked to numerous malignancies, including breast cancers. The prostate derived Ets transcription factor (PDEF) is reported to be a breast and prostate tumor-associated Ets factor. To understand the roles of PDEF in breast cancers, we transiently overexpressed PDEF in MDA-MB-231 human breast cancer cells by adenoviral-mediated gene delivery. PDEF binding protein complexes were isolated by immunoprecipitation and PDEF-interacting proteins were analyzed by LC-MS/MS. After subtracting the proteins binding nonspecifically to antibody-bead complexes, we identified 286 proteins in the PDEF-associated protein complex. By comparison to published protein-protein interactions, we selected 121 proteins for further analysis. PDEF interactors distribute not only in the nucleus, but also in the cytoplasm, as well as other subcellular compartments. Our data reveals that PDEF interacts with a variety of proteins involved in cell cycle, DNA repair, cytoskeleton organization, mRNA processing, tRNA biosynthesis, protein folding, and cell signaling. Furthermore, the EGFR1- (Erbb1) and Erbb2- (HER2) related proteins erbin, an ERBB2 interacting protein, catenin delta-1 (which interacts with Erbin), and EGFR (a HER2-homology receptor) were associated with PDEF. These findings indicate that PDEF may be regulated by Erbb2 or EGFR-activated signaling pathways in breast cancer cells. Further analysis of these proteins will identify the roles of PDEF-interacting proteins in breast tumorigenesis.
机译：Ets蛋白是转录因子家族，共有85个氨基酸保守的DNA结合结构域ETS结构域。 27种已知的人类Ets转录因子控制着多种生物学过程，包括细胞增殖，分化，凋亡，血管生成，转化和侵袭。一些Ets基因的过度表达与包括乳腺癌在内的许多恶性肿瘤有关。据报道，前列腺衍生的Ets转录因子（PDEF）是与乳房和前列腺肿瘤相关的Ets因子。为了了解PDEF在乳腺癌中的作用，我们通过腺病毒介导的基因传递在MDA-MB-231人乳腺癌细胞中短暂过表达PDEF。通过免疫沉淀分离PDEF结合蛋白复合物，并通过LC-MS / MS分析与PDEF相互作用的蛋白。减去非特异性结合抗体-珠复合物的蛋白质后，我们在PDEF相关的蛋白质复合物中鉴定了286个蛋白质。通过与已发表的蛋白质-蛋白质相互作用进行比较，我们选择了121种蛋白质进行进一步分析。 PDEF相互作用子不仅分布在细胞核中，而且分布在细胞质以及其他亚细胞区室中。我们的数据表明，PDEF与多种蛋白质相互作用，这些蛋白质参与细胞周期，DNA修复，细胞骨架组织，mRNA加工，tRNA生物合成，蛋白质折叠和细胞信号传导。此外，EGFR1-（Erbb1）和Erbb2-（HER2）相关蛋白erbin，ERBB2相互作用蛋白，catenin delta-1（与Erbin相互作用）和EGFR（HER2同源受体）与PDEF相关。这些发现表明，PDEF可能受乳腺癌细胞中Erbb2或EGFR激活的信号通路的调节。这些蛋白质的进一步分析将确定与PDEF相互作用的蛋白质在乳腺肿瘤发生中的作用。

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