Structure and expression of the human gene for the matrix metalloproteinase matrilysin.
Structure and expression of the human gene for the matrix metalloproteinase matrilysin.
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DOI：
10.1016/s0021-9258(17)42131-4
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发表时间：
1994-01
期刊：
影响因子：
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通讯作者：
M. Gaire;Z. Magbanua;S. Mcdonnell;L. McNeil;D. Lovett;L. Matrisian
中科院分区：
文献类型：
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作者：
M. Gaire;Z. Magbanua;S. Mcdonnell;L. McNeil;D. Lovett;L. Matrisian
基质溶素是基质金属蛋白酶家族的一员，由于缺乏保守的COOH末端蛋白结构域而在结构上不同于其他基质金属蛋白酶。此外，基质溶解素mRNA在正常和恶性组织中以特定和不同的方式调节。对人类基质溶素基因的基因组结构的分析显示，前五个外显子的组织在基质金属蛋白酶家族的不同成员之间是高度保守的，但是基质溶素包含非典型的第六个外显子。基质溶解素基因的启动子区具有在几个其他基质金属蛋白酶家族成员中保守的几个特征，包括TATA、AP-1和PEA 3元件的存在。比较人基质溶素启动子与大鼠基质溶素启动子/氯霉素乙酰转移酶构建体在HeLa细胞中的表达，揭示含有AP-1和PEA 3元件的构建体对表皮生长因子和肿瘤启动子的响应相似（12-O-十四酰基-佛波醇-13-乙酸酯）诱导，但是上游基质溶解素序列的加入导致了上游基质溶解素序列没有观察到的转录活性的增加。基质溶解素和其他金属蛋白酶的启动子之间观察到的相似性和差异，可以提供洞察的分子机制，调节这个家庭的酶作为一个整体的表达和区分个别家庭成员的表达模式的因素。
Matrilysin, a member of the matrix metalloproteinase family, is structurally different from the other matrix metalloproteinases by virtue of the absence of a conserved COOH-terminal protein domain. In addition, matrilysin mRNA is regulated in a specific and distinct manner in normal and malignant tissues. Analysis of the genomic structure of the human matrilysin gene revealed that the organization of the first five exons is highly conserved among the different members of the matrix metalloproteinase family, but that matrilysin contains an atypical sixth exon. The promoter region of the matrilysin gene has several features that are conserved among several other matrix metalloproteinase family members, including the presence of TATA, AP-1, and PEA3 elements. Comparison of the expression of the human matrilysin promoter with rat stromelysin promoter/chloramphenicol acetyltransferase constructs in HeLa cells revealed that constructs containing AP-1 and PEA3 elements respond similarly to epidermal growth factor and tumor promoter (12-O-tetradecanoyl-phorbol-13-acetate) induction, but that the addition of upstream stromelysin sequences results in an increased transcriptional activity not observed with upstream matrilysin sequences. The similarities and differences observed between the promoters of matrilysin and the other metalloproteinases may provide insights into the molecular mechanisms that regulate the expression of this family of enzymes as a whole and the factors that distinguish the expression patterns of individual family members.