SMURF2 facilitates ubiquitin-mediated degradation of ID2 to attenuate lung cancer cell proliferation.
SMURF2 facilitates ubiquitin-mediated degradation of ID2 to attenuate lung cancer cell proliferation.
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SMURF2促进泛素介导的ID2降解，从而抑制肺癌细胞的增殖。
DOI：
10.7150/ijbs.80979
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发表时间：
2023
影响因子：
9.2
通讯作者：
Jiang J
中科院分区：
文献类型：
--
作者：
Han M;Guo Y;Li Y;Zeng Q;Zhu W;Jiang J
smad特异性E3泛素蛋白连接酶2 （SMURF2）在多种肿瘤中起肿瘤启动子或肿瘤抑制子的作用。然而，SMURF2对非小细胞肺癌的具体作用尚未完全了解。本研究分析SMURF2的表达及其诊断价值。采用共免疫沉淀法（Co-IP）、近接法（PLA）、染色质免疫沉淀法（ChIP）和裸鼠荷瘤模型进一步阐明SMURF2在肺癌中的作用。SMURF2在NSCLC患者的肿瘤组织中表达降低，高SMURF2表达与良好预后显著相关。此外，SMURF2的过表达显著抑制肺癌细胞的进展。机制上，SMURF2与DNA结合2抑制剂（ID2）相互作用，随后通过泛素-蛋白酶体途径促进ID2的多泛素化和降解。肺细胞中ID2的下调会解离细胞周期蛋白依赖性激酶抑制剂p21的正调节因子内源性转录因子E2A，最终在肺癌细胞中诱导G1/S阻滞。本研究表明，通过SMURF2调控ID2可能控制肿瘤进展，有助于开发新的靶向抗肿瘤药物。
SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) functions as either a tumor promoter or tumor suppressor in several tumors. However, the detailed effect of SMURF2 on non-small cell lung cancer has not been fully understood. In this study, SMURF2 expression and its diagnostic value were analyzed. Co-Immunoprecipitation (Co-IP), proximity ligation assay (PLA), chromatin immunoprecipitation (ChIP) and nude mice tumor-bearing model were applied to further clarify the role of SMURF2 in lung cancer. SMURF2 expression was reduced in the tumor tissues of patients with NSCLC and high SMURF2 expression was significantly correlated with favorable outcomes. Furthermore, the overexpression of SMURF2 significantly inhibited lung cancer cell progression. Mechanistically, SMURF2 interacted with inhibitor of DNA binding 2 (ID2), subsequently promoting the poly-ubiquitination and degradation of ID2 through the ubiquitin-proteasome pathway. Downregulated ID2 in lung cells dissociates endogenous transcription factor E2A, a positive regulator of the cyclin-dependent kinase inhibitor p21, and finally induces G1/S arrest in lung cancer cells. This study revealed that the manipulation of ID2 via SMURF2 may control tumor progression and contribute to the development of novel targeted antitumor drugs.
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影响因子：
7.4
作者：
Kijewska, Magdalena;Viski, Carmen;Isacke, Clare M.
通讯作者：
Isacke, Clare M.
DOI：
10.1084/jem.20151426
发表时间：
2016-03-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hu H;Wang H;Xiao Y;Jin J;Chang JH;Zou Q;Xie X;Cheng X;Sun SC
通讯作者：
Sun SC
影响因子：
64.5
作者：
BENEZRA, R;DAVIS, RL;WEINTRAUB, H
通讯作者：
WEINTRAUB, H
DOI：
10.1186/s13058-022-01504-4
发表时间：
2022-01-25
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Deshpande RP;Sharma S;Liu Y;Pandey PR;Pei X;Wu K;Wu SY;Tyagi A;Zhao D;Mo YY;Watabe K
通讯作者：
Watabe K
剪接因子 SRSF1 通过 PTPMT1 的致癌剪接转换促进乳腺癌进展
DOI：
10.1186/s13046-021-01978-8
发表时间：
2021-05-15
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Du JX;Luo YH;Zhang SJ;Wang B;Chen C;Zhu GQ;Zhu P;Cai CZ;Wan JL;Cai JL;Chen SP;Dai Z;Zhu W
通讯作者：
Zhu W