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Molecular structure, gene expression and functional role of WFDC1 in angiogenesis and cancer
Cell Biochemistry and Function ( IF 2.8 ) Pub Date : 2021-02-21 , DOI: 10.1002/cbf.3624
Sipin Zhu 1, 2 , Lin Ye 3 , Samuel Bennett 2 , Huazi Xu 1 , Dengwei He 3 , Jiake Xu 1, 2
Affiliation  

Whey acidic proteins (WAP) perform a diverse range of important biological functions, including proteinase activity, calcium transport and bacterial growth. The WAP four-disulphide core domain protein 1 (WFDC1) gene (also called PS20), encodes the 20 kDa prostate stromal protein (ps20), which is a member of the WAP-type four-disulphide core domain family of proteins, and exhibits characteristics of serine protease inhibitors, such as elafin and secretory leukocyte protease inhibitor. Molecular structural analysis reveals that ps20 consists of four-disulphide bonds formed by eight cysteine residues located at the carboxyl terminus of the protein. Wfdc1-null mice were found to display no overt developmental phenotype, suggesting a dispensable role in organ growth and development. However, WFDC1 was able to mediate endothelial cell migration and pericyte stabilization, which are vital for the formation of functional vascular structures. WFDC1 was also found to be downregulated in cancers and exhibited a regulatory effect on cell proliferation. In addition, it was involved in the modulation of memory T cells during human immunodeficiency virus infection. Gaining a solid understanding of the mechanisms by which WFDC1 regulates tissue homeostasis and disease processes, in a tissue specific manner, will be an important move towards the development of WFDC1/ps20 as potential therapeutic targets.

中文翻译:

WFDC1在血管生成和癌症中的分子结构、基因表达和功能作用

乳清酸性蛋白 (WAP) 具有多种重要的生物学功能,包括蛋白酶活性、钙转运和细菌生长。WAP 四二硫核心域蛋白 1 (WFDC1) 基因(也称为 PS20)编码 20 kDa 前列腺基质蛋白 (ps20),它是 WAP 型四二硫核心域蛋白家族的成员,并表现出丝氨酸蛋白酶抑制剂的特性,如弹性蛋白和分泌性白细胞蛋白酶抑制剂。分子结构分析表明,ps20 由位于蛋白质羧基末端的八个半胱氨酸残基形成的四个二硫键组成。发现 Wfdc1-null 小鼠没有表现出明显的发育表型,这表明在器官生长和发育中发挥了可有可无的作用。然而,WFDC1 能够介导内皮细胞迁移和周细胞稳定,这对于功能性血管结构的形成至关重要。还发现 WFDC1 在癌症中被下调并对细胞增殖表现出调节作用。此外,它还参与了人类免疫缺陷病毒感染期间记忆 T 细胞的调节。深入了解 WFDC1 以组织特异性方式调节组织稳态和疾病过程的机制,将是开发 WFDC1/ps20 作为潜在治疗靶点的重要举措。它参与了人类免疫缺陷病毒感染期间记忆 T 细胞的调节。深入了解 WFDC1 以组织特异性方式调节组织稳态和疾病过程的机制,将是开发 WFDC1/ps20 作为潜在治疗靶点的重要举措。它参与了人类免疫缺陷病毒感染期间记忆 T 细胞的调节。深入了解 WFDC1 以组织特异性方式调节组织稳态和疾病过程的机制,将是开发 WFDC1/ps20 作为潜在治疗靶点的重要举措。
更新日期:2021-02-21
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