FBPs are calibrated molecular tools to adjust gene expression
FBPs are calibrated molecular tools to adjust gene expression
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DOI：
10.1128/mcb.00754-06
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发表时间：
2006-09-01
影响因子：
5.3
通讯作者：
Levens, David
中科院分区：
文献类型：
--
作者：
Chung, Hye-Jung;Liu, Juhong;Levens, David
FUSE结合蛋白（far-upstream element，FBP）家族的三个成员在基因调控中具有不同的功能。因此，他们进行了各种生化，分子生物学和细胞生物学测试，以评估是否他们的序列差异反映功能定制或中性变化在p53残基。每一个FBP表现出的特征性的内部转录激活和抑制，与蛋白质的合作伙伴，和亚细胞运输的结合。虽然一些差异，如减弱的FBP 3核定位，是可预测的主要序列差异，出乎意料的失败FBP 3结合的FBP-interacting阻遏物（FIR）被追溯到看似保守的取代内的一小块N-末端α-螺旋。FBPs的反式激活强度和FIR结合强度的顺序相反。尽管它们具有显着的特征和不同的活性，但FBP的交通共享亚核位点并调节许多共同的靶基因，包括c-myc。虽然各种各样的功能已归因于FBPs，基于他们的面板的共享和独特的功能，我们建议，他们构成一个分子调控试剂盒，通过一个共同的机制来调整共享的目标的表达。
The three far-upstream element (FUSE) binding protein (FBP) family members have been ascribed different functions in gene regulation. They were therefore examined with various biochemical, molecular biological, and cell biological tests to evaluate whether their sequence differences reflect functional customization or neutral changes at unselected residues. Each FBP displayed a characteristic profile of intrinsic transcription activation and repression, binding with protein partners, and subeellular trafficking. Although some differences, such as weakened FBP3 nuclear localization, were predictable from primary sequence differences, the unexpected failure of FBP3 to bind the FBP-interacting repressor (FIR) was traced to seemingly conservative substitutions within a small patch of an N-terminal alpha-helix. The transactivation strength and the FIR-binding strength of the FBPs were in the opposite order. Despite their distinguishing features and differential activities, the FBP`s traffic to shared subnuclear sites and regulate many common target genes, including c-myc. Though a variety of functions have been attributed to the FBPs, based upon their panel of shared and unique features, we propose that they constitute a molecular regulatory kit that tunes the expression of shared targets through a common mechanism.