当前位置: X-MOL 学术Nat. Chem. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
An infection-induced oxidation site regulates legumain processing and tumor growth
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2022-03-24 , DOI: 10.1038/s41589-022-00992-x
Yekaterina Kovalyova 1, 2, 3 , Daniel W Bak 4 , Elizabeth M Gordon 1, 2 , Connie Fung 5 , Jennifer H B Shuman 6 , Timothy L Cover 6, 7 , Manuel R Amieva 5, 8 , Eranthie Weerapana 4 , Stavroula K Hatzios 1, 2, 3
Affiliation  

Oxidative stress is a defining feature of most cancers, including those that stem from carcinogenic infections. Reactive oxygen species can drive tumor formation, yet the molecular oxidation events that contribute to tumorigenesis are largely unknown. Here we show that inactivation of a single, redox-sensitive cysteine in the host protease legumain, which is oxidized during infection with the gastric cancer-causing bacterium Helicobacter pylori, accelerates tumor growth. By using chemical proteomics to map cysteine reactivity in human gastric cells, we determined that H. pylori infection induces oxidation of legumain at Cys219. Legumain oxidation dysregulates intracellular legumain processing and decreases the activity of the enzyme in H. pylori-infected cells. We further show that the site-specific loss of Cys219 reactivity increases tumor growth and mortality in a xenograft model. Our findings establish a link between an infection-induced oxidation site and tumorigenesis while underscoring the importance of cysteine reactivity in tumor growth.



中文翻译:

感染诱导的氧化位点调节legumain加工和肿瘤生长

氧化应激是大多数癌症的一个决定性特征,包括那些源于致癌感染的癌症。活性氧可以驱动肿瘤形成,但导致肿瘤发生的分子氧化事件在很大程度上是未知的。在这里,我们展示了宿主蛋白酶legumain中单个氧化还原敏感半胱氨酸的失活,该蛋白酶在感染引起胃癌的细菌幽门螺杆菌期间被氧化,加速了肿瘤的生长。通过使用化学蛋白质组学来绘制人胃细胞中半胱氨酸的反应性,我们确定幽门螺杆菌感染会在 Cys219 处诱导豆类蛋白酶的氧化。Legumain 氧化失调细胞内的legumain 加工并降低幽门螺杆菌中酶的活性-感染的细胞。我们进一步表明,Cys219 反应性的位点特异性丧失会增加异种移植模型中的肿瘤生长和死亡率。我们的研究结果建立了感染诱导的氧化位点与肿瘤发生之间的联系,同时强调了半胱氨酸反应性在肿瘤生长中的重要性。

更新日期:2022-03-24
down
wechat
bug