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首页> 外文期刊>Cell cycle >A nuclear targeting determinant for SATB1, a genome organizer in the T cell lineage.
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A nuclear targeting determinant for SATB1, a genome organizer in the T cell lineage.

机译：SATB1（T细胞谱系中的基因组组织者）的核靶向决定子。

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SATB1 is a nuclear protein, which acts as a cell-type specific genome organizer and gene regulator essential for T cell differentiation and activation. Several functional domains of SATB1 have been identified. However, the region required for nuclear localization remains unknown. To delineate this region, we employed sequence analysis to identify phylogenetically diverse members of the SATB1 protein family, and used hidden Markov model (HMM)-based analysis to define conserved regions and motifs in this family. One of the regions conserved in SATB1- and SATB2-like proteins in mammals, fish, frog and bird, is located near the N-terminus of family members. We found that the N-terminus of human SATB1 was essential for the nuclear localization of the protein. Furthermore, fusing residues 20-40 to a cytoplasmic green fluorescence protein (GFP) fused to pyruvate kinase (PK) was sufficient to quantitatively translocate the pyruvate kinase into the nucleus. The nuclear targeting sequence of human SATB1 (residues 20-40) is novel and does not contain clusters of basic residues, typically found in 'classical' nuclear localization signals (NLSs). We investigated the importance of four well-conserved residues (Lys29, Arg32, Glu34, and Asn36) in this nuclear targeting sequences. Remarkably, full-length SATB1 harboring a single point mutation at either Lys29 or Arg32, but not Glu34 or Asn36, did not enter the nucleus. Our results indicate that SATB1 N-terminal residues 20-40 represent a novel determinant of nuclear targeting.
机译：SATB1是一种核蛋白，充当T细胞分化和激活必不可少的细胞类型特异性基因组组织者和基因调节剂。已经确定了SATB1的几个功能域。但是，核定位所需的区域仍然未知。为了描述该区域，我们使用序列分析来识别SATB1蛋白家族的系统发育多样性成员，并使用基于隐马尔可夫模型（HMM）的分析来定义该家族中的保守区域和基序。在哺乳动物，鱼类，青蛙和鸟类中，在SATB1和SATB2类蛋白中保守的区域之一位于家庭成员的N端附近。我们发现人SATB1的N端对于蛋白质的核定位至关重要。此外，将残基20-40融合到与丙酮酸激酶（PK）融合的胞质绿色荧光蛋白（GFP）足以定量地将丙酮酸激酶转移到细胞核中。人SATB1的核靶向序列（残基20-40）是新颖的，不包含通常在“经典”核定位信号（NLS）中发现的碱性残基簇。我们研究了在该核靶向序列中四个保守性好的残基（Lys29，Arg32，Glu34和Asn36）的重要性。值得注意的是，全长SATB1在Lys29或Arg32处具有单点突变，但在Glu34或Asn36处没有单点突变，因此没有进入核。我们的结果表明，SATB1 N末端残基20-40代表核靶向的新决定因素。

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