HUMAN X-BOX-BINDING PROTEIN-1 IS REQUIRED FOR THE TRANSCRIPTION OF A SUBSET OF HUMAN CLASS-II MAJOR HISTOCOMPATIBILITY GENES AND FORMS A HETERODIMER WITH C-FOS

HUMAN X-BOX-BINDING PROTEIN-1 IS REQUIRED FOR THE TRANSCRIPTION OF A SUBSET OF HUMAN CLASS-II MAJOR HISTOCOMPATIBILITY GENES AND FORMS A HETERODIMER WITH C-FOS
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DOI:
10.1073/pnas.88.10.4309
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发表时间:
1991-05-01
影响因子:
11.1
通讯作者:
GLIMCHER, LH
GLIMCHER, LH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
ONO, SJ;LIOU, HC;GLIMCHER, LH

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最近描述了编码亮氨酸拉链类蛋白质(人X盒结合蛋白,hXBP-1)的一个成员的互补DNA,所述蛋白质结合到HLA-HLA主要组织相容性复合体基因的保守X盒(X2)的3'末端。 进一步的凝胶阻滞分析表明,hXBP-1也结合HLA-DPB X2,但不结合其他X2序列。 以反义方向插入hXBP-1 cDNA的哺乳动物表达载体的瞬时转染抑制Raji细胞中HLA-DR和HLA-DP的表面表达。 与对照反义载体共转染的细胞相比,反义hXBP-1载体与HLA-DQB/氯霉素乙酰转移酶(但不是HLA-DQB/氯霉素乙酰转移酶)报告质粒的共转染降低了Raji细胞和γ-干扰素处理的HeLa细胞中氯霉素乙酰转移酶的活性。 此外,hXBP-1显示与c-fos原癌基因的产物形成稳定的异源二聚体。 这些数据表明,hXBP-1的c-fos异源二聚体是至关重要的人类II类主要组织相容性复合体基因的一个子集的转录和不同的II类基因的调控机制是不同的。
A complementary DNA encoding a member of the leucine-zipper class of proteins (human X-box-binding protein, hXBP-1) that binds to the 3' end of the conserved X box (X2) of the HLA-DRA major histocompatibility complex gene was recently described. Further gel-retardation analysis has demonstrated that hXBP-1 also binds to HLA-DPB X2 but not to other X2 sequences. Transient transfection of a mammalian expression vector with the hXBP-1 cDNA inserted in the antisense orientation represses the surface expression of HLA-DR and HLA-DP in Raji cells. Cotransfection of the antisense hXBP-1 vector with a HLA-DRA/chloramphenicol acetyltransferase (but not a HLA-DQB/chloramphenicol acetyltransferase) reporter plasmid decreases chloramphenicol acetyltransferase activity in Raji cells and in gamma-interferon-treated HeLa cells relative to cells cotransfected with a control antisense vector. Moreover, hXBP-1 is shown to form a stable heterodimer with the product of the c-fos protooncogene. These data suggest that the hXBP-1 c-fos heterodimer is critical for the transcription of a subset of the human class II major histocompatibility complex genes and that the regulatory mechanisms for the different class II genes are distinct.