The mouse BP-1 gene: structure, chromosomal localization, and regulation of expression by type I interferons and interleukin-7.
The mouse BP-1 gene: structure, chromosomal localization, and regulation of expression by type I interferons and interleukin-7.
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小鼠 BP-1 基因：结构、染色体定位以及 I 型干扰素和白细胞介素 7 的表达调节。
DOI：
10.1006/geno.1996.0180
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发表时间：
1996
期刊：
影响因子：
4.4
通讯作者：
Cooper,MD
中科院分区：
文献类型：
--
作者：
Wang,J;Walker,H;Lin,Q;Jenkins,N;Copeland,NG;Watanabe,T;Burrows,PD;Cooper,MD
BP-1/6C 3抗原是在未成熟B系细胞、骨髓基质细胞、胸腺皮质上皮细胞、内皮细胞、肠上皮细胞和肾近端小管细胞上表达的同源二聚体、磷酸化II型膜整合糖蛋白。生物化学和分子分析鉴定BP-1为谷氨酰氨肽酶，一种催化调节肽氨基末端酸性氨基酸残基水解的胞外酶。我们分离了编码BP-1基因（基因符号Enpep）的基因组克隆。该基因跨度超过110 kb，包含20个外显子。除了第一个和最后一个外显子外，它由56至171 bp的小外显子组成，这些外显子被小于100 bp至约10 kb的内含子分开。锌结合基序HEXXH和下游19个氨基酸的谷氨酸残基（也结合锌）在外显子5和6中编码。引物延伸分析揭示了一个共同的主要转录起始位点在前B细胞系，在骨髓基质细胞系，和肾细胞。启动子区含有TATA样元件和淋巴细胞特异性转录因子的潜在DNA结合基序，包括Ikaros、BSAP、PU. 1和八聚体结合蛋白，以及几种普遍存在的转录因子的DNA结合基序。也位于启动子区的干扰素应答元件似乎是功能性的，因为I型干扰素（IFN-α/IFN-β）上调前B细胞系中BP-1的表达。一个2.1 kb的启动子片段，当融合到荧光素酶报告基因，能够驱动荧光素酶的表达在前B细胞，通常表达BP-1，并在Ag 8细胞，其中BP-1的表达被扑灭。BP-1/Enpep基因定位于小鼠3号染色体的远端区域，与人染色体4 q25同源。有趣的是，虽然白细胞介素-7（IL-7）诱导细胞生长并增加BP-1表达，但IFN-α/IFN-β上调BP-1表达，但抑制IL-7诱导的增殖。这一发现表明，上调的BP-1表达可以与细胞生长信号分离。
The BP-1/6C3 antigen is a homodimeric, phosphorylated type II membrane integral glycoprotein expressed on immature B-lineage cells, bone marrow stromal cells, thymic cortical epithelial cells, endothelial cells, enterocytes, and renal proximal tubular cells. Biochemical and molecular analysis identified BP-1 as glutamyl aminopeptidase, an ectoenzyme that catalyzes the hydrolysis of acidic amino acid residues from the amino termini of regulatory peptides. We have isolated genomic clones that encode theBP-1gene (gene symbolEnpep). The gene spans more than 110 kb and contains 20 exons. Except for the first and the last exons, it is composed of small exons ranging from 56 to 171 bp that are separated by introns ranging from less than 100 bp to approximately 10 kb. The zinc binding motif HEXXH and the glutamic acid residue 19 amino acids downstream, which also binds zinc, are encoded in exons 5 and 6. Primer extension analysis revealed a common major transcriptional start site in a pre-B cell line, in a bone marrow stromal cell line, and in kidney cells. The promoter region contains a TATA-like element and potential DNA-binding motifs for lymphocyte-specific transcription factors including Ikaros, BSAP, PU.1, and octamer binding proteins, as well as DNA binding motifs for several ubiquitous transcription factors. An interferon responsive element also located in the promoter region appeared to be functional, since type I interferons (IFN-α/IFN-β) upregulated BP-1 expression in pre-B cell lines. A 2.1-kb promoter fragment, when fused to a luciferase reporter gene, was able to drive luciferase expression in pre-B cells, which normally express BP-1, and in Ag8 cells, in which BP-1 expression is extinguished. TheBP-1/Enpepgene was localized to a distal region of mouse chromosome 3 in a region homologous to human chromosome 4q25. Interestingly, while interleukin-7 (IL-7) induced both cell growth and increased BP-1 expression, IFN-α/IFN-β upregulated BP-1 expression but inhibited IL-7-induced proliferation. This finding indicates that the upregulated BP-1 expression can be disassociated from the cell growth signal.