MUTATIONAL ANALYSIS OF THE CONSERVED BASIC DOMAIN OF HUMAN IMMUNODEFICIENCY VIRUS TAT PROTEIN

MUTATIONAL ANALYSIS OF THE CONSERVED BASIC DOMAIN OF HUMAN IMMUNODEFICIENCY VIRUS TAT PROTEIN
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DOI:
10.1128/jvi.63.3.1181-1187.1989
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发表时间:
1989-03-01
影响因子:
5.4
通讯作者:
CULLEN, BR
CULLEN, BR
中科院分区:
医学2区
文献类型:
--
作者:
HAUBER, J;MALIM, MH;CULLEN, BR

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由已知灵长类免疫缺陷病毒株编码的 tat 反式激活因子共享一个保守的高碱性蛋白结构域。此处显示人类免疫缺陷病毒1型tat基因中的该序列的诱变减少但不是消除人类免疫缺陷病毒1型特异性基因表达的反式激活。抑制程度以剂量依赖性方式变化,并且在低水平的tat表达时最为明显。人们发现tat基本结构域的多个突变会损害tat蛋白的体内稳定性和核定位。据推测,该蛋白质结构域用于有效地将tat基因产物靶向表达细胞核内的适当位点或底物。
The tat trans-activators encoded by the known strains of primate immunodeficiency virus share a conserved, highly basic protein domain. Mutagenesis of this sequence in the tat gene of human immunodeficiency virus type 1 is shown here to reduce, but not eliminate, the trans-activation of human immunodeficiency virus type 1-specific gene expression. The degree of inhibition is shown to vary in a dose-dependent manner and is most marked at low levels of tat expression. Multiple mutations of the basic domain of tat were found to impair both the in vivo stability and the nuclear localization of the tat protein. It is proposed that this protein domain serves to efficiently target the tat gene product to its appropriate site or substrate within the nucleus of expressing cells.