A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene family is regulated during G1 progression, mitogenic stimulation, differentiation, and senescence.
A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene family is regulated during G1 progression, mitogenic stimulation, differentiation, and senescence.
复制标题
人类组织金属蛋白酶抑制剂 (TIMP) 基因家族的一个新成员在 G1 进展、有丝分裂刺激、分化和衰老过程中受到调节。
DOI：
--
复制
发表时间：
1994
影响因子：
4.8
通讯作者：
R. Müller
中科院分区：
文献类型：
--
作者：
M. Wick;C. Bürger;S. Brüsselbach;Lucibello Fc;R. Müller
我们已经确定在人二倍体成纤维细胞系WI-38中的一种新的血清诱导基因，丝裂原诱导基因5（mig-5），延迟早期类，这代表了一个新成员的家庭的人组织金属蛋白酶抑制剂（TIMPs）。推导的Mig-5蛋白与鸡TIMP-3具有最高程度的同源性（74%的同一性），并且与人TIMP-1和TIMP-2的同源性更远（30-38%的同一性），表明Mig-5可能代表鸡TIMP-3的人同源物。与TIMP-1和TIMP-2相反，mig-5 mRNA的表达不仅响应于促有丝分裂刺激而被诱导，而且在正常增殖的WI-38成纤维细胞和HL-60骨髓细胞中也受到细胞周期调节，在中期G1附近显示出明显的峰值。与这一观察结果一致，HL-60细胞分化为粒细胞或巨噬细胞样细胞导致mig-5 mRNA水平增加，并伴有G1期阻滞。相反，衰老的人成纤维细胞中的mig-5表达降低，表明这些细胞可能在最大mig-5表达阶段之前或之后的G1阶段被阻断。由于与绝大多数其他已知的丝裂原诱导基因相反，mig-5的表达在G1期周期性上调，该基因应代表用于分析细胞周期进程、终末分化和复制性衰老的宝贵工具。
We have identified in the human diploid fibroblast cell line WI-38 a novel serum-inducible gene, mitogen-inducible gene 5 (mig-5), of the delayed-early class, which represents a new member of the family of human tissue inhibitors of metalloproteinases (TIMPs). The deduced Mig-5 protein shares the highest degree of homology with chicken TIMP-3 (74% identity) and is more distantly related to human TIMP-1 and TIMP-2 (30-38% identity), indicating that mig-5 may represent the human homolog of chicken TIMP-3. In contrast to TIMP-1 and TIMP-2, mig-5 mRNA expression is not only induced in response to mitogenic stimulation but also is subject to cell cycle regulation in normally proliferating WI-38 fibroblasts and HL-60 myeloid cells, showing a clear peak around mid-G1. In agreement with this observation, differentiation of HL-60 cells to either granulocytic or macrophage-like cells leads to increased levels of mig-5 mRNA concomitant with a block in G1. In contrast, mig-5 expression is decreased in senescent human fibroblasts, suggesting that these cells may be blocked at a stage in G1 before or after the phase of maximum mig-5 expression. Since in contrast to the vast majority of other known mitogen-inducible genes, mig-5 expression is periodically up-regulated in G1, this gene should represent an invaluable tool for the analysis of cell cycle progression, terminal differentiation, and replicative senescence.