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首页> 外文期刊>Cell discovery. >A novel ER–microtubule-binding protein, ERLIN2, stabilizes Cyclin B1 and regulates cell cycle progression
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A novel ER–microtubule-binding protein, ERLIN2, stabilizes Cyclin B1 and regulates cell cycle progression

机译：一种新型的ER-微管结合蛋白ERLIN2可稳定Cyclin B1并调节细胞周期进程

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The gene encoding endoplasmic reticulum (ER) lipid raft-associated protein 2 (ERLIN2) is amplified in human breast cancers. ERLIN2 gene mutations were also found to be associated with human childhood progressive motor neuron diseases. Yet, an understanding of the physiological function and mechanism for ERLIN2 remains elusive. In this study, we reveal that ERLIN2 is a spatially and temporally regulated ER–microtubule-binding protein that has an important role in cell cycle progression by interacting with and stabilizing the mitosis-promoting factors. Whereas ERLIN2 is highly expressed in aggressive human breast cancers, during normal development ERLIN2 is expressed at the postnatal stage and becomes undetectable in adulthood. ERLIN2 interacts with the microtubule component α-tubulin, and this interaction is maximal during the cell cycle G2/M phase where ERLIN2 simultaneously interacts with the mitosis-promoting complex Cyclin B1/Cdk1. ERLIN2 facilitates K63-linked ubiquitination and stabilization of Cyclin B1 protein in G2/M phase. Downregulation of ERLIN2 results in cell cycle arrest, represses breast cancer proliferation and malignancy and increases sensitivity of breast cancer cells to anticancer drugs. In summary, our study revealed a novel ER–microtubule-binding protein, ERLIN2, which interacts with and stabilizes mitosis-promoting factors to regulate cell cycle progression associated with human breast cancer malignancy.
机译：编码内质网（ER）脂筏相关蛋白2（ERLIN2）的基因在人类乳腺癌中被扩增。 ERLIN2基因突变也被发现与人类儿童进行性运动神经元疾病有关。然而，对ERLIN2的生理功能和机制的了解仍然难以捉摸。在这项研究中，我们揭示了ERLIN2是一种时空调节的ER-微管结合蛋白，它通过与有丝分裂促进因子相互作用并使其稳定来在细胞周期进程中发挥重要作用。 ERLIN2在侵略性人乳腺癌中高表达，而在正常发育过程中，ERLIN2在出生后阶段表达，成年后则无法检测到。 ERLIN2与微管成分α-微管蛋白相互作用，这种相互作用在细胞周期G2 / M阶段最大，其中ERLIN2同时与促进有丝分裂的复杂细胞周期蛋白B1 / Cdk1相互作用。 ERLIN2在G2 / M期促进K63连接的泛素化和细胞周期蛋白B1蛋白的稳定。 ERLIN2的下调导致细胞周期停滞，抑制乳腺癌的扩散和恶性肿瘤，并增加乳腺癌细胞对抗癌药物的敏感性。总之，我们的研究揭示了一种新型的ER-微管结合蛋白ERLIN2，该蛋白与有丝分裂促进因子相互作用并稳定有丝分裂促进因子，以调节与人类乳腺癌恶性肿瘤相关的细胞周期进程。

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