Characterization of a family of novel cysteine- serine-rich nuclear proteins (CSRNP).

Characterization of a family of novel cysteine- serine-rich nuclear proteins (CSRNP).
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新型富含半胱氨酸-丝氨酸的核蛋白 (CSRNP) 家族的表征。

DOI:
10.1371/journal.pone.0000808
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发表时间:
2007-08-29
期刊:
影响因子:
3.7
通讯作者:
Ihle, James N.
Ihle, James N.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gingras, Sebastien;Pelletier, Stephane;Boyd, Kelli;Ihle, James N.

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基因阵列分析已被广泛用于鉴定T细胞活化过程中诱导的基因。我们的研究鉴定了小鼠T细胞中响应于IL-2强烈诱导的立即早期基因,我们将其命名为富含半胱氨酸丝氨酸的核蛋白-1(CSRNP-1)。人类直系同源物先前被鉴定为AXIN 1诱导基因(AXUD 1)。该蛋白不包含在公共数据库中注释的序列定义的结构域或基序,然而该基因是共享保守区域的三个哺乳动物基因家族的成员,包括富含半胱氨酸和丝氨酸的区域和碱性结构域,它们编码核蛋白,具有转录激活结构域并结合序列AGAGTG。因此,我们建议命名为CSRNP-1,-2和-3的家庭。为了阐明CSRNP-1、CSRNP-2和CSRNP-3的生理功能,我们通过在胚胎干细胞中同源重组来产生这些基因中的每一个的缺陷小鼠。虽然CSRNP蛋白具有转录因子的标志,并且CSRNP-1的表达被IL-2高度诱导,但是单个基因的缺失对正常小鼠发育、造血或T细胞功能没有明显的后果。然而,合并缺陷导致部分新生儿死亡,这表明基因具有冗余功能。
Gene array analysis has been widely used to identify genes induced during T cell activation. Our studies identified an immediate early gene that is strongly induced in response to IL-2 in mouse T cells which we named cysteine- serine-rich nuclear protein-1 (CSRNP-1). The human ortholog was previously identified as an AXIN1 induced gene (AXUD1). The protein does not contain sequence defined domains or motifs annotated in public databases, however the gene is a member of a family of three mammalian genes that share conserved regions, including cysteine- and serine-rich regions and a basic domain, they encode nuclear proteins, possess transcriptional activation domain and bind the sequence AGAGTG. Consequently we propose the nomenclature of CSRNP-1, -2 and -3 for the family. To elucidate the physiological functions of CSRNP-1, -2 and -3, we generated mice deficient for each of these genes by homologous recombination in embryonic stem cells. Although the CSRNP proteins have the hallmark of transcription factors and CSRNP-1 expression is highly induced by IL-2, deletion of the individual genes had no obvious consequences on normal mouse development, hematopoiesis or T cell functions. However, combined deficiencies cause partial neonatal lethality suggesting that the genes have redundant functions.
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