CLONING AND EXPRESSION ANALYSIS OF THE MURINE LYMPHOTOXIN BETA-GENE
CLONING AND EXPRESSION ANALYSIS OF THE MURINE LYMPHOTOXIN BETA-GENE
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DOI：
10.1073/pnas.92.3.674
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发表时间：
1995-01-31
影响因子：
11.1
通讯作者：
NEDOSPASOV, SA
中科院分区：
文献类型：
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作者：
POKHOLOK, DK;MAROULAKOU, IG;NEDOSPASOV, SA
肿瘤坏死因子α（TNF-α）和可溶性光敏素（LT）（也称为LT-α或TNF-β）是具有相似生物活性的细胞因子，由相关和紧密连锁的基因编码。TNF-α是炎症反应的介质，以可溶性和跨膜形式存在。LT-α可以通过与33-kDa跨膜亚基LT-β结合而分泌或保留在细胞表面。最近克隆的人LT-β基因编码另一个TNF家族成员，并与主要组织相容性复合体基因座内的TNF/LT基因座相连。细胞表面LT是由LT-α和LT-β组成的异源三聚体，其生理功能尚未明确定义。我们现在报告了小鼠LT-β基因的基因组区域和cDNA的序列分析，该基因与小鼠主要组织相容性复合体基因座内的TNF-α和LT-α基因密切相关。与含有四个外显子的TNF-α、LT-α和人LT-β基因不同，鼠LT-β含有三个外显子，并编码具有66个氨基酸插入物的244个氨基酸的多肽，这在人同源物中是不存在的。原位杂交证实LT-β在淋巴和造血组织中的组成性表达。LT-β转录在胸腺髓质和脾白色髓中最大。LT-β mRNA也在皮肤和大脑的特定区域中检测到。LT-β启动子区含有推定的Ets结合位点，表明LT-β的表达可能部分受Ets转录因子的调节，其淋巴表达模式与LT-β重叠。
Tumor necrosis factor alpha (TNF-alpha) and soluble lymphotoxin (LT) (also called LT-alpha or TNF-beta) are cytokines with similar biological activities that are encoded by related and closely linked genes. TNF-alpha, a mediator of the inflammatory response, exists in soluble and transmembrane forms. LT-alpha can be secreted or retained at the cell surface by binding to a 33-kDa transmembrane subunit, LT-beta. The recently cloned human LT-beta gene encodes another TNF family member and is linked to the TNF/LT locus within the major histocompatibility complex locus. The cell surface LT is a heterotrimer consisting of LT-alpha and LT-beta, whose physiological function is not yet clearly defined. We now report the sequence analysis of the genomic region and cDNA of murine LT-beta gene, which is closely associated with the TNF-alpha and LT-alpha genes within the murine major histocompatibility complex locus. Unlike the TNF-alpha, LT-alpha, and human LT-beta genes, which contain four exons, the murine LT-beta contains three exons and encodes a 244-amino acid polypeptide with a 66-amino acid insert that is absent from the human homologue. In situ hybridization demonstrates constitutive expression of LT-beta in lymphoid and hematopoietic tissues. LT-beta transcription is maximal in the thymic medulla and in splenic white pulp. LT-beta mRNA is also detected in the skin and in specific regions of the brain. The LT-beta promoter region contains putative Ets-binding sites, suggesting that the expression of LT-beta may be regulated in part by Ets transcription factors whose pattern of lymphoid expression overlaps that of LT-beta.