GTP binding by class II transactivator: Role in nuclear import

GTP binding by class II transactivator: Role in nuclear import
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DOI:
10.1126/science.285.5432.1402
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发表时间:
1999-08-27
期刊:
影响因子:
56.9
通讯作者:
Ting, JPY
Ting, JPY
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Harton, JA;Cressman, DE;Ting, JPY

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第二类反式激活因子(CIITA)是人类白细胞抗原-D(人类白细胞抗原-D)基因的全球转录共激活因子。CIITA含有类似于三磷酸鸟苷(CTP)结合蛋白的基序。这份报告表明,CIITA与GTP结合,这些基序的突变降低了它的GTP结合和反式激活活性。用RAS中的类似序列替换这些基序可以恢复CIITA功能。CIITA表现出很少的GTPase活性,但CIITA中赋予GTPase活性的突变降低了转录活性。CITA对GTP的结合与核进口有关。因此,与其他GTP结合蛋白不同,CIITA参与转录激活,利用GTP结合促进自身的核进口。
Class II transactivator (CIITA) is a global transcriptional coactivator of human Leukocyte antigen-D (HLA-D) genes. CIITA contains motifs similar to guanosine triphosphate (CTP)-binding proteins. This report shows that CIITA binds GTP, and mutations in these motifs decrease its GTP-binding and transactivation activity. Substitution of these motifs with analogous sequences from Ras restores CIITA function. CIITA exhibits little GTPase activity, yet mutations in CIITA that confer GTPase activity reduce transcriptional activity. GTP binding by CIITA correlates with nuclear import. Thus, unlike other GTP-binding proteins, CIITA is involved in transcriptional activation that uses GTP binding to facilitate its own nuclear import.