<br>NLRP11 蛋白在肺腺癌早期将组蛋白赖氨酸乙酰转移酶 KAT7 桥接至乙酰化波形蛋白,Advanced Science

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NLRP11 蛋白在肺腺癌早期将组蛋白赖氨酸乙酰转移酶 KAT7 桥接至乙酰化波形蛋白
Advanced Science ( IF 14.3 ) Pub Date : 2023-07-09 , DOI: 10.1002/advs.202300971
Rui Yang _{1,

2} , Weilin Peng _{3,

4} , Shuai Shi _{3,

4} , Xiong Peng _{3,

4} , Qidong Cai _{3,

4} , Zhenyu Zhao _{3,

4} , Boxue He _{3,

4} , Guangxu Tu _{3,

4} , Wei Yin _{3,

4} , Yichuan Chen ₅ , Yuqian Zhang ₆ , Fang Liu ₇ , Xiang Wang _{3,

4} , Desheng Xiao _{1,

2} , Yongguang Tao _{1,

2,

3,

4}

Affiliation

波形蛋白的积累是上皮-间质转化（EMT）的核心事件。据广泛报道，翻译后修饰在赋予波形蛋白不同的特性和功能方面发挥着至关重要的作用。在此，鉴定了一种在第¹⁰⁴位赖氨酸乙酰化的波形蛋白 (vimentin-K104Ac) 的新修饰，该修饰在肺腺癌细胞 (LUAD) 中稳定。从机制上讲，炎症反应的调节因子 NACHT、LRR 和 PYD 结构域蛋白 11 (NLRP11) 与波形蛋白结合并促进波形蛋白-K104Ac 表达，该表达在 LUAD 早期阶段高表达，并且经常出现在波形蛋白中。 LUAD 组织呈阳性。此外，还观察到乙酰转移酶赖氨酸乙酰转移酶 7 (KAT7) 与 NLRP11 和波形蛋白结合，直接介导波形蛋白在 Lys ¹⁰⁴处的乙酰化，并且 NLRP11 可以诱导 KAT7 的细胞质定位。波形蛋白-K104Q 转染介导的恶性促进明显大于波形蛋白-WT 转染介导的恶性促进。此外，抑制 NLRP11 和 KAT7 对波形蛋白的影响可显着抑制波形蛋白阳性 LUAD 在体内和体外的恶性行为。总之，这些发现建立了炎症与 EMT 之间的关系，这通过依赖于 NLRP11 的 KAT7 介导的波形蛋白第¹⁰⁴位赖氨酸的乙酰化反映出来。

"点击查看英文标题和摘要"

The NLRP11 Protein Bridges the Histone Lysine Acetyltransferase KAT7 to Acetylate Vimentin in the Early Stage of Lung Adenocarcinoma

Accumulation of vimentin is the core event in epithelial–mesenchymal transition (EMT). Post-translational modifications have been widely reported to play crucial roles in imparting different properties and functions to vimentin. Here, a novel modification of vimentin, acetylated at Lys¹⁰⁴ (vimentin-K104Ac) is identified, which is stable in lung adenocarcinoma (LUAD) cells. Mechanistically, NACHT, LRR, and PYD domain-containing protein 11 (NLRP11), a regulator of the inflammatory response, bind to vimentin and promote vimentin-K104Ac expression, which is highly expressed in the early stages of LUAD and frequently appears in vimentin-positive LUAD tissues. In addition, it is observed that an acetyltransferase, lysine acetyltransferase 7 (KAT7), which binds to NLRP11 and vimentin, directly mediates the acetylation of vimentin at Lys¹⁰⁴ and that the cytoplasmic localization of KAT7 can be induced by NLRP11. Malignant promotion mediated by transfection with vimentin-K104Q is noticeably greater than that mediated by transfection with vimentin-WT. Further, suppressing the effects of NLRP11 and KAT7 on vimentin noticeably inhibited the malignant behavior of vimentin-positive LUAD in vivo and in vitro. In summary, these findings have established a relationship between inflammation and EMT, which is reflected via KAT7-mediated acetylation of vimentin at Lys¹⁰⁴ dependent on NLRP11.

更新日期：2023-07-09

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