Journal Article

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

Xiao, Desheng, Shi, Shuai, Chen, Yichuan, Tao, Yongguang, Yin, Wei, Cai, Qidong, Wang, Xiang, He, Boxue, Zhao, Zhenyu, Yang, Rui, Tu, Guangxu, Zhang, Yuqian, Peng, Xiong, Peng, Weilin, Liu, Fang

2023

Overview

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. Under normal conditions, vimentin is degraded by ubiquitin‐proteasome pathway. In cancer cells persistently expressing NLRP11, KAT7 tends to translocate from the nucleus to the cytoplasm and is recruited to bind with vimentin by NLRP11, resulting in vimentin acetylation at K104 and inhibition of ubiquitin‐independent proteasomal degradation, thereby contributing to the malignant phenotype related to epithelial–mesenchymal transition in LUAD cells.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Adenocarcinoma of Lung - pathology / Cell adhesion & migration / Cell cycle / Chromatography / Cytokines / epithelial–mesenchymal transition / Genes / Histone Acetyltransferases / Histones - metabolism / Humans / Lung cancer / Lung Neoplasms - metabolism / Lysine - metabolism / Mass spectrometry / Medical diagnosis / Medical prognosis / Metastasis / non‐histone acetylation / Pathogens / Phosphorylation / Proteins / Scientific imaging / tumorigenesis / Vimentin - metabolism / Viral infections