Different requirements for signal transducer and activator of transcription 1α and interferon regulatory factor 1 in the regulation of low molecular mass polypeptide 2 and transporter associated with antigen processing 1 gene expression
Different requirements for signal transducer and activator of transcription 1α and interferon regulatory factor 1 in the regulation of low molecular mass polypeptide 2 and transporter associated with antigen processing 1 gene expression
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DOI：
10.1074/jbc.273.26.16177
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发表时间：
1998-06-26
影响因子：
4.8
通讯作者：
Ferrone, S
中科院分区：
文献类型：
--
作者：
Chatterjee-Kishore, M;Kishore, R;Ferrone, S
抗原加工机制的组成部分，即低分子量多肽 (LMP) 2 和与抗原加工相关的转运蛋白 (TAP) 1，由主要组织相容性复合体 II 类亚区内紧密相连的基因编码。尽管这两个基因共享一个双向启动子，但 LMP2 和 TAP1 具有差异的细胞表达。 TAP1 是组成型表达的。然而，在大多数细胞中，LMP2 的表达需要干扰素-γ 的诱导。 LMP2/TAP1启动子内的调节元件以及结合这些元件的转录因子已经被定义，然而，这些反式激活因子如何调节差异性TAP1和LMP2基因转录尚不清楚。我们通过分析三种具有不同 LMP2 和 TAP1 表达表型的人类黑色素瘤细胞系解决了这个问题。虽然干扰素调节因子 1 或 Stat1 与重叠的干扰素共有序列-2/GAS 的结合足以调节 TAP1 基因的转录，但 LMP2 基因转录需要这两个因子的结合。将野生型 Stat1 α 或干扰素调节因子 1 cDNA 转染至缺乏这些转录因子的细胞后，LMP2 基因转录的恢复支持了这一结论。 TAP1基因调节的灵活性可能反映了其在维持免疫监视中的作用。此外，静止人类细胞中 LMP2 基因转录的缺乏表明 LMP2 表达反映了细胞激活的状态。
The components of the antigen processing machinery, low molecular mass polypeptide (LMP) 2 and transporter associated with antigen processing (TAP) 1, are encoded by closely linked genes within the major histocompatibility complex class II subregion. Although the two genes share a bi-directional promoter, LMP2 and TAP1 have differential cellular expression. TAP1 is expressed constitutively. However, LMP2 expression requires induction by interferon-gamma in most cells. The regulatory elements within the LMP2/TAP1 promoter and the transcription factors that bind these elements have been defined, However, how these transactivators regulate differential TAP1 and LMP2 gene transcription is not known. We have addressed this question by analyzing three human melanoma cell lines with distinct phenotypes of LMP2 and TAP1 expression.Whereas binding of either interferon regulatory factor 1 or Stat1 to the overlapping interferon consensus sequence-2/GAS is sufficient for regulating transcription of the TAP1 gene, binding of both factors is required for LMP2 gene transcription. This conclusion is supported by restoration of LMP2 gene transcription following transfection of wild type Stat1 alpha or interferon regulatory factor 1 cDNA into cells lacking these transcription factors. The flexibility in the regulation of the TAP1 gene may reflect its role in maintaining immune surveillance. Furthermore, lack of LMP2 gene transcription in quiescent human cells suggests that LMP2 expression reflects a state of cell activation.