Open AccessISGylation of EMD promotes its interaction with PDHA to inhibit aerobic oxidation in lung adenocarcinoma
Author(s) -
Zhang Congcong,
Cui Jiangtao,
Cao Leiqun,
Tian Xiaoting,
Miao Yayou,
Wang Yikun,
Qiu Shiyu,
Guo Wanxin,
Ma Lifang,
Xia Jinjing,
Zhang Xiao
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17536
Subject(s) - downregulation and upregulation , serine , phosphorylation , carcinogenesis , chemistry , glycolysis , microbiology and biotechnology , cancer research , biology , biochemistry , metabolism , gene
Abnormal nuclear structure caused by dysregulation of skeletal proteins is a common phenomenon in tumour cells. However, how skeletal proteins promote tumorigenesis remains uncovered. Here, we revealed the mechanism by which skeletal protein Emerin (EMD) promoted glucose metabolism to induce lung adenocarcinoma (LUAD). Firstly, we identified that EMD was highly expressed and promoted the malignant phenotypes in LUAD. The high expression of EMD might be due to its low level of ubiquitination. Additionally, the ISGylation at lysine 37 of EMD inhibited lysine 36 ubiquitination and upregulated EMD stability. We further explored that EMD could inhibit aerobic oxidation and stimulate glycolysis. Mechanistically, via its β‐catenin interaction domain, EMD bound with PDHA, stimulated serine 293 and 300 phosphorylation and inhibited PDHA expression, facilitated glycolysis of glucose that should enter the aerobic oxidation pathway, and EMD ISGylation was essential for EMD‐PDHA interaction. In clinical LUAD specimens, EMD was negatively associated with PDHA, while positively associated with EMD ISGylation, tumour stage and diameter. In LUAD with higher glucose level, EMD expression and ISGylation were higher. Collectively, EMD was a stimulator for LUAD by inhibiting aerobic oxidation via interacting with PDHA. Restricting cancer‐promoting role of EMD might be helpful for LUAD treatment.