The structure and regulation of the human and mouse matrix metalloproteinase-21 gene and protein

The structure and regulation of the human and mouse matrix metalloproteinase-21 gene and protein
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DOI:
10.1042/bj20030174
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发表时间:
2003-06-01
影响因子:
4.1
通讯作者:
Strongin, AY
Strongin, AY
中科院分区:
生物学3区
文献类型:
--
作者:
Marchenko, GN;Marchenko, ND;Strongin, AY

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基质金属蛋白酶(MMPs)在正常发育的组织重塑中起着关键作用,特别是在从恶性肿瘤到中风的疾病中。我们克隆并彻底表征了新的人类和小鼠MMP基因编码MMP-21。MMP-21是人类基因组编码的最后一种未表征的MMP。人和小鼠MMP-21是非洲爪蟾X-MMP的直向同源物。MMP-21的潜在酶原(569个氨基酸残基)由前结构域、催化结构域和血红素样结构域组成,并且潜在地能够在其分泌途径中被弗林蛋白酶样前蛋白转化酶激活至细胞外环境。人MMP-21可能是Wnt通路的靶基因。此外,MMP-21的表达由已知对器官发生至关重要的Pax和Notch转录因子独特地控制。MMP-21在小鼠胚胎发生中瞬时表达,并在胚胎神经元组织中增加。我们的观察清楚地表明,MMP-21在胚胎发生中具有重要的特异性功能,尤其是在神经元细胞中。
Matrix metalloproteinases (MMPs) play key roles in tissue remodelling under normal development and, especially, in diseases ranging from malignancies to stroke. We cloned and thoroughly characterized the novel human and mouse MMP gene encoding MMP-21. MMP-21 is the last uncharacterized MMP coded by the human genome. Human and mouse MMP-21 is the orthologue of Xenopus laevis X-MMP. The latent proenzyme of MMP-21 (569 amino acid residues) consists of the prodomain, the catalytic domain and the haemopexin-like domain, and is potentially capable of being activated in its secretory pathway to the extracellular milieu by furin-like proprotein convertases. INTRODUCTION Human MMP-21 is the probable target gene of the Wnt pathway. In addition, the expression of MMP-21 is controlled uniquely by Pax and Notch transcription factors known to be critical for organogenesis. MMP-21 is expressed transiently in mouse embryogenesis and increased in embryonic neuronal tissues. Our observations clearly indicate that there is an important specific function for MMP-21 in embryogenesis, especially in neuronal cells.