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首页> 外文期刊>EMBO Journal >C-TERMINAL ACTIVATING AND INHIBITORY DOMAINS DETERMINE THE TRANSACTIVATION POTENTIAL OF BSAP (PAX-5), PAX-2 AND PAX-8
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C-TERMINAL ACTIVATING AND INHIBITORY DOMAINS DETERMINE THE TRANSACTIVATION POTENTIAL OF BSAP (PAX-5), PAX-2 AND PAX-8

机译：c端激活和抑制域确定TRANSACTIVATION BSAP的潜力(PAX-5) PAX-2 PAX-8

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摘要

Pax-5 encodes the transcription factor BSAP which plays an essential role in early B cell development and midbrain patterning. In this study we have analysed the structural requirements for transcriptional activation by BSAP. In vitro mutagenesis and transient transfection experiments indicate that the C-terminal serine/threonine/proline-rich region of BSAP contains a potent transactivation domain of 55 amino acids which is active from promoter and enhancer positions. This transactivation domain was found to be inactivated by a naturally occurring frameshift mutation in one PAX-5 allele of the acute lymphoblastic leukemia cell line REH. The function of the transactivation domain is negatively regulated by adjacent sequences from the extreme C-terminus. The activating and inhibitory domains function together as an independent regulatory module in different cell types as shown by fusion to the GAL4 DNA binding domain. The same arrangement of positively and negatively acting sequences has been conserved in the mammalian Pax-2 and Pax-8, the zebrafish Pax-b as well as the sea urchin Pax-258 proteins. These data demonstrate that the transcriptional competence of a subfamily of Pax proteins is determined by a C-terminal regulatory module composed of activating and inhibitory sequences.
机译：Pax-5编码转录因子BSAP哪个在早期的B细胞中扮演着重要的角色发展和中脑模式。研究分析了结构转录激活的要求BSAP。转染实验表明c端丝氨酸/苏氨酸脯氨酸BSAP含有强有力的transactivation域55个氨基酸的启动子活性和增强器的位置。域自然被发现灭活发生在一个PAX-5等位基因移码突变急性淋巴细胞白血病细胞系盐土。负受相邻序列从极端的糖。抑制域作为一个函数在一起独立管理模块在不同的细胞类型如图所示通过融合GAL4 DNA结合域。负面作用一直在保守序列哺乳动物Pax-2 Pax-8,斑马鱼Pax-b以及海胆pax - 258蛋白质。这些数据表明,转录能力Pax蛋白的一个亚科由一个c端管理模块激活和抑制组成的序列。

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