NOVEL METALLOPROTEINASE INHIBITORS--ROLE IN TUMOR INVASION AND METASTASIS

新型金属蛋白酶抑制剂——在肿瘤侵袭和转移中的作用

• 批准号: 3813434
• 负责人: W G STETLER-STEVENSON
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813434
• 关键词: binding proteins; collagenase; complementary DNA; cysteine; enzyme substrate; genetic transcription; human tissue; melanoma; metalloenzyme; metastasis; molecular cloning; neoplasm /cancer invasiveness; neoplastic cell; oncoproteins; protease inhibitor; stoichiometry; zymogens

We have isolated and characterized the complete primary structure of a new member of the tissue inhibitor of metalloproteinase family (TIMP family) which we refer to as TIMP-2. TIMP-2 binds specifically to the latent form of the 72 kDa type IV collagenase. Inhibition of the activated enzyme occurs with 1:1 molar stoichiometry. TIMP-2 contains 12 cysteine residues, the positions of which are highly conserved when compared with the primary structure of TIMP-1. We have obtained a 1.0 kB cDNA clone which encodes for the pro-TIMP-2. This clone encodes for a 194 amino acid mature TIMP-2 molecule and a 26 amino acid signal peptide. Recent studies have focused on the production of recombinant TIMP-2 and transcriptional regulation of the TIMP-2 transcript levels.

我们分离并鉴定了一个新的 金属蛋白酶组织抑制剂家族（TIMP家族）成员 我们称之为TIMP-2。TIMP-2特异性结合潜伏型 72 kDa的IV型胶原酶。抑制活化酶 以1：1的摩尔化学计量发生。TIMP-2含有12个半胱氨酸残基， 其位置与原代相比高度保守， TIMP-1的结构我们获得了一个1.0 kB的cDNA克隆，它编码 TIMP-2前体该克隆编码194个氨基酸的成熟TIMP-2 分子和26个氨基酸的信号肽。最近的研究集中在 重组TIMP-2的产生和TIMP-2基因的转录调控 TIMP-2转录水平。