THE IKAROS GENE ENCODES A FAMILY OF FUNCTIONALLY DIVERSE ZINC-FINGER DNA-BINDING PROTEINS
THE IKAROS GENE ENCODES A FAMILY OF FUNCTIONALLY DIVERSE ZINC-FINGER DNA-BINDING PROTEINS
复制标题
DOI：
10.1128/mcb.14.12.8292
复制
发表时间：
1994-12-01
影响因子：
5.3
通讯作者：
GEORGOPOULOS, K
中科院分区：
文献类型：
--
作者：
MOLNAR, A;GEORGOPOULOS, K
我们以前描述过淋巴细胞限制性Ikaros基因编码锌指dna结合蛋白，作为淋巴细胞承诺和分化的潜在调节因子。在这里，我们报道了另外四个Ikaros转录本的分离，它们是交替剪接的产物，编码功能多样的蛋白质。Ikaros蛋白含有独特的锌指模块组合，这决定了它们的整体序列特异性和亲和力。Ik-1和Ik-2蛋白都可以结合，尽管具有不同的亲和力，但存在于许多淋巴细胞特异性调节元件中的相同识别序列。Ik-3和Ik-4蛋白仅与这些基序的一个子集相互作用。Ik-1和Ik-2蛋白能强烈刺激转录，而Ik-3和Ik-4是弱激活因子。值得注意的是，Ikaros蛋白的转录激活电位与其亚细胞定位相关。Ikaros亚型在非淋巴样细胞中异位表达时，Ik-1和Ik-2定位于细胞核，而Ik-3和Ik-4主要存在于细胞质中。Ikaros亚型在淋巴细胞中的表达存在差异：Ik-1和Ik-2 mrna是主要形式，Ik-4仅在早期t细胞祖细胞中大量存在，而Ik-3和Ik-5转录本在淋巴细胞发育过程中表达水平相对较低。Ikaros基因能够产生功能多样的蛋白质，这些蛋白质可能参与不同的调节途径，这证实了它在淋巴细胞发育过程中作为主要调节剂的作用。
We previously described the lymphocyte-restricted Ikaros gene encoding a zinc finger DNA-binding protein as a potential regulator of lymphocyte commitment and differentiation. Here, we report the isolation of four additional Ikaros transcripts, products of alternate splicing that encode functionally diverse proteins. The Ikaros proteins contain unique combinations of zinc finger modules that dictate their overall sequence specificity and affinity. The Ik-1 and Ik-2 proteins can both bind, albeit with different affinities, to the same recognition sequences present in a number of lymphocyte-specific regulatory elements. The Ik-3 and the Ik-4 proteins interact only with a subset of these motifs. The Ik-1 and Ik-2 proteins can strongly stimulate transcription, whereas Ik-3 and Ik-4 are weak activators. Significantly, the transcription activation potential of the Ikaros proteins correlates with their subcellular localization. Upon ectopic expression of the Ikaros isoforms in nonlymphoid cells, Ik-1 and Ik-2 localize to the nucleus, whereas Ik-3 and Ik-4 are predominantly found in the cytoplasm. The Ikaros isoforms are expressed differentially in lymphocytes: Ik-1 and Ik-2 mRNAs are the predominating forms, and Ik-4 is present in significant amounts only in early T-cell progenitors, whereas Ik-3 and Ik-5 transcripts are expressed at relatively low levels throughout lymphocyte development. The ability of the Ikaros gene to generate functionally diverse proteins that may participate in distinct regulatory pathways substantiates its role as a master regulator during lymphocyte development.