MICAL-L2 Is Essential for c-Myc Deubiquitination and Stability in Non-small Cell Lung Cancer Cells.
MICAL-L2 Is Essential for c-Myc Deubiquitination and Stability in Non-small Cell Lung Cancer Cells.
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MICAL-L2 对于非小细胞肺癌细胞中的 c-Myc 去泛素化和稳定性至关重要
DOI：
10.3389/fcell.2020.575903
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发表时间：
2020
影响因子：
5.5
通讯作者：
Du J
中科院分区：
文献类型：
--
作者：
Min P;Zhang L;Wang Y;Qi C;Song Y;Bibi M;Zhang Y;Ma Y;Zhao X;Yu M;Du J
MICAL- l2是与CasL （micical）家族相互作用的分子中的一员，据报道在几种类型的癌症中高表达，然而，MICAL- l2在NSCLC发病机制中的作用仍有待探索。本研究旨在阐明MICAL-L2参与NSCLC细胞增殖的机制。材料与方法：采用免疫组化染色法检测MICAL-L2在人肺癌组织中的表达水平。用siRNA或质粒转染细胞来调节MICAL-L2的表达。EdU染色和CCK-8检测细胞增殖。Western blotting检测MICAL-L2和磷酸化/总c-Myc表达。通过免疫荧光染色、Western blotting和共免疫沉淀法评估MICAL-L2与c-Myc的相互作用。采用Western blotting、多泛素化检测和蛋白稳定性试验评估MICAL-L2是否通过c-Myc发挥其致癌作用。结果：MICAL-L2在人NSCLC中高表达。MICAL-L2过表达增加了非小细胞肺癌细胞的增殖，MICAL-L2缺失则降低了非小细胞肺癌细胞的增殖，这种效应与细胞周期阻滞有关。MICAL-L2与c-Myc蛋白相互作用，维持细胞核c-Myc水平并延长其半衰期。MICAL-L2表达的下调通过加速c-Myc的多泛素化导致c-Myc蛋白稳定性降低，并导致c-Myc降解。我们进一步发现MICAL-L2去泛素化c-Myc并阻断其降解，可能是通过抑制c-Myc苏氨酸残基58的磷酸化。结论：这些结果表明MICAL-L2是细胞核中c-Myc去泛素化和稳定性的关键调节因子，该活性可能参与促进NSCLC细胞增殖。
Objectives: MICAL-L2, a member of the molecules interacting with the CasL (MICAL) family, was reported to be highly expressed in several types of cancers, however, the roles of MICAL-L2 in NSCLC pathogenesis remain to be explored. This study is designed to clarify the mechanisms by which MICAL-L2 participates in NSCLC cell proliferation. Materials and Methods: The expression levels of MICAL-L2 in human lung cancer samples were assessed by immunohistochemical staining. Cells were transfected with siRNA or plasmids to regulate MICAL-L2 expression. Cell proliferation was measured by EdU staining and CCK-8 assays. MICAL-L2 and phosphorylated/total c-Myc expression were examined by Western blotting analysis. Interaction between MICAL-L2 and c-Myc was assessed by immunofluorescence staining, Western blotting and co-immunoprecipitation assays. Western blotting, polyubiquitylation detection and protein stability assays were used to assess whether MICAL-L2 exerts its oncogenic effect via c-Myc. Results: We found that MICAL-L2 was highly expressed in human NSCLC. While overexpressing MICAL-L2 increased NSCLC cell proliferation, MICAL-L2 depletion decreased the proliferation of NSCLC cells, an effect that was linked to cell cycle arrest. MICAL-L2 physically interacted with the c-Myc protein and functioned to maintain nuclear c-Myc levels and prolonged its half-life. Knockdown of MICAL-L2 expression led to decreased c-Myc protein stability through accelerating polyubiquitylation of c-Myc and gave rise to c-Myc degradation. We further found that MICAL-L2 deubiquitinated c-Myc and blocked its degradation, presumably by inhibiting c-Myc phosphorylation at threonine residue 58. Conclusions: These results indicate that MICAL-L2 is a key regulator of c-Myc deubiquitination and stability in the nucleus, and this activity may be involved in promoting NSCLC cell proliferation.
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影响因子：
3.3
作者：
Sun Y;Jaldin-Fincati J;Liu Z;Bilan PJ;Klip A
通讯作者：
Klip A
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影响因子：
8.2
作者：
Liu, Hong;Zhao, Wu-li;Shao, Rong-guang
通讯作者：
Shao, Rong-guang
MICAL1 通过调节乳腺癌细胞的氧化应激来控制细胞侵袭表型
影响因子：
3.8
作者：
Deng W;Wang Y;Gu L;Duan B;Cui J;Zhang Y;Chen Y;Sun S;Dong J;Du J
通讯作者：
Du J
DOI：
10.1083/jcb.201407068
发表时间：
2015-03-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ioannou MS;Bell ES;Girard M;Chaineau M;Hamlin JN;Daubaras M;Monast A;Park M;Hodgson L;McPherson PS
通讯作者：
McPherson PS
影响因子：
5.5
作者：
Roy NH;Burkhardt JK
通讯作者：
Burkhardt JK