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三元复合因子Elk-1、SAP-1a和SAP-2(ERP/NET)的比较分析

Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET).

作者信息

Price M A, Rogers A E, Treisman R

机构信息

Transcription Laboratory, Imperial Cancer Research Fund, London, UK.

出版信息

EMBO J. 1995 Jun 1;14(11):2589-601. doi: 10.1002/j.1460-2075.1995.tb07257.x.

Abstract

A transcription factor ternary complex composed of Serum Response Factor (SRF) and Ternary Complex Factor (TCF) mediates the response of the c-fos Serum Response Element (SRE) to growth factors and mitogens. Three Ets domain proteins, Elk-1, SAP-1 and ERP/NET, have been reported to have the properties of TCF. Here we compare Elk-1 and SAP-1a with the human ERP/NET homologue SAP-2. All three TCF RNAs are ubiquitously expressed at similar relative levels. All three proteins contain conserved regions that interact with SRF and the c-fos SRE with comparable efficiency, but in vitro complex formation by SAP-2 is strongly inhibited by its C-terminal sequences. Similarly, only Elk-1 and SAP-1a efficiently bind the c-fos SRE in vivo; ternary complex formation by SAP-2 is weak and is substantially unaffected by serum stimulation or v-ras co-expression. All three TCFs contain C-terminal transcriptional activation domains that are phosphorylated following growth factor stimulation. Activation requires conserved S/T-P motifs found in all the TCF family members. Each TCF activation domain can be phosphorylated in vitro by partially purified ERK2, and ERK activation in vivo is sufficient to potentiate transcriptional activation.

摘要

由血清反应因子(SRF)和三元复合因子(TCF)组成的转录因子三元复合物介导了c-fos血清反应元件(SRE)对生长因子和有丝分裂原的反应。据报道,三种Ets结构域蛋白,即Elk-1、SAP-1和ERP/NET,具有TCF的特性。在此,我们将Elk-1和SAP-1a与人类ERP/NET同源物SAP-2进行比较。所有三种TCF RNA均以相似的相对水平在全身广泛表达。所有三种蛋白质都含有与SRF和c-fos SRE相互作用的保守区域,其效率相当,但SAP-2在体外形成复合物受到其C端序列的强烈抑制。同样,只有Elk-1和SAP-1a在体内能有效结合c-fos SRE;SAP-2形成三元复合物的能力较弱,且基本不受血清刺激或v-ras共表达的影响。所有三种TCF都含有C端转录激活结构域,在生长因子刺激后会发生磷酸化。激活需要在所有TCF家族成员中都存在的保守S/T-P基序。每个TCF激活结构域在体外都可被部分纯化的ERK2磷酸化,且体内ERK激活足以增强转录激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f9/398373/0497956e6b33/emboj00035-0200-a.jpg

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