加列-3结合蛋白抑制细胞外肝素6-O-内硫酸酶硫-2的发生
Aswini Panigrahi1, Julius Benicky1, Reem Aljuhani2
1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA; Clinical and Translational Glycoscience Research Center, Georgetown University, Washington, District of Columbia, USA.
Molecular & cellular proteomics : MCP
|June 2, 2024
概括
硫-2,一种与头部和部癌症的不良结果相关的酶,直接与加勒-3结合蛋白 (LG3BP) 相互作用. 这种相互作用,受到氏丁硫酸盐对硫-2,抑制硫-2活动和HNSCC细胞入侵的影响.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 硫-1和硫-2是关键酶,在人类中修改肝硫酸蛋白质糖 (HSPG).
- 硫-2-与癌症致癌性有关,并且与头部和部状细胞癌 (HNSCC) 的低生存率有关.
- 瘤微环境中的硫-2的蛋白质与蛋白质相互作用尚未得到充分理解.
研究的目的:
- 为了确定HNSCC中硫-2的直接结合伙伴.
- 研究瘤微环境中硫-2相互作用的功能后果.
主要方法:
- 使用单克隆抗体 (mAb) 亲和力净化与质谱学相结合.
- 再组合蛋白被用于体外相互作用的验证.
- 用局部定向的突变发生法来产生一个缺乏CS的硫-2突变体.
主要成果:
- 鉴定出加列-3结合蛋白 (LG3BP) 是硫-2的特定结合伙伴.
- 发现与硫酸二化合物共价连接的里丁硫酸盐 (CS) 链会影响LG3BP结合.
- 在体外,LG3BP以剂量依赖的方式抑制了硫-2-酶的活性.
- 添加LG3BP减少了球形培养中的HNSCC细胞入侵.
结论:
- LG3BP是硫-2.0的新型结合伙伴.
- 由CS调节的硫-2和LG3BP之间的相互作用在调节硫-2活性方面发挥作用.
- 这种相互作用可能会通过影响硫-2在瘤微环境中的作用来影响HNSCC的进展.
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