NRF2 regulates EGF stability through OTUD4 in lung adenocarcinoma

被引：0

作者：

Hu, Shuming ^{[1
]}

Yuan, Yuan ^{[1
,2
]}

Yan, Ruihan ^{[1
]}

Xie, Huikang ^{[2
]}

Cai, Rong ^{[1
]}

Xu, Jiaqian ^{[1
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai, Peoples R China

[2] Tongji Univ, Shanghai Pulm Hosp, Dept Pathol, Sch Med, Shanghai 200433, Peoples R China

[3] Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Sch Med, Shanghai 200025, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2024年 / 708卷

基金：

中国国家自然科学基金;

关键词：

NRF2; Lung adenocarcinoma; EGF; OTUD4; Ubiquitination; DUAL ROLES; CANCER; MUTATIONS; PROVIDES;

D O I：

10.1016/j.bbrc.2024.149798

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

NRF2 (NFE2L2) is a transcription factor mainly for regulating cellular antioxidant response and therefore promotes tumor progression. The target genes of NRF2 also play important roles in cellular processes including glucose metabolism, de novo serine synthesis, iron metabolism, etc. Here, by modulating NRF2 expression in lung adenocarcinoma (LUAD) cells, we showed that NRF2 regulated EGF expression at protein level. Furthermore, EGF was identified as a ubiquitinated protein. We predicted three deubiquitinases of EGF, and OTUD4 had the highest correlation with NRF2 in LUAD among the three. OTUD4 expression was reduced upon NRF2 knockingdown and recovered upon NRF2 rescuing in A549 cells. Then a potential binding site for NRF2 in OTUD4 promoter was searched out. By binding with OTUD4 promoter, NRF2 transcriptionally activated OTUD4, thus promoted EGF deubiquitination and enhanced its stability. More importantly, OTUD4 and NRF2 expression was found being correlated in LUAD patients. The data collectively revealed a novel mechanism of NRF2 regulating on EGF stability through OTUD4 in LUAD.

引用

页数：8

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