Covalent CDK7 Inhibitor THZ1 Inhibits Myogenic Differentiation.
Covalent CDK7 Inhibitor THZ1 Inhibits Myogenic Differentiation.
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DOI：
10.7150/jca.25395
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发表时间：
2018
影响因子：
3.9
通讯作者：
Long C
中科院分区：
文献类型：
--
作者：
Ma X;Kuang X;Xia Q;Huang Z;Fan Y;Ning J;Wen J;Zhang H;Yan J;Zhang Q;Shen H;Long C
CDK7共价抑制剂THZ 1是一种新发现的抗肿瘤药物，THZ 1通过抑制CDK7影响转录因子TFIIH的功能，进而影响RNA聚合酶II，最终影响转录起始。研究发现THZ 1对多种肿瘤细胞株具有抑制增殖和促进凋亡的作用。然而，没有关于THZ 1在正常组织中的潜在副作用的报道。在癌症过程中，恶病质的肌肉消耗需要通过肌细胞的分化来补充。然而，THZ1对肌源性分化的影响仍不清楚。本研究发现THZ 1能抑制C2C12细胞和小鼠原代成肌细胞的分化，并抑制分化相关转录因子和肌细胞结构蛋白如myh3、myogenin和MCK的表达。THZ 1可抑制C2C12细胞增殖和迁移，增加其氧化应激，促进其凋亡。我们的数据表明THZ 1抑制肌源性分化，这表明基于THZ 1的疗法可能对肌肉功能有潜在的副作用。
Covalent CDK7 inhibitor THZ1 is a newly discovered anti-tumor drug.THZ1 affects the function of transcription factor TFIIH by inhibiting CDK7, which in turn affects RNA polymerase II, and ultimately affects transcription initiation. Study found that THZ1 could inhibit proliferation and promote apoptosis of several tumor cell lines. However, there is no report of the potential side effect of THZ1 in normal tissues. In the course of cancer, the muscle consumption of cachexia needs to be supplemented by the differentiation of muscle cells. However, the effect of THZ1 on myogenic differentiation remains unclear. Our study in this article found that THZ1 could both inhibit the differentiation of C2C12 cells and mouse primary myoblasts, also repressing the expression of differentiation-related transcription factors and muscle structural proteins, such as and myogenin, myh3 and MCK. Moreover, THZ1 could inhibit C2C12 cell proliferation and migration, increase its oxidative stress and promote its apoptosis. Our data indicates that THZ1 inhibits myogenic differentiation, suggesting that therapies based on THZ1 might have potential side effects on muscle functions.
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人 TFIIH 激酶 CDK7 调节转录相关的染色质修饰。
影响因子：
8.8
作者：
Ebmeier CC;Erickson B;Allen BL;Allen MA;Kim H;Fong N;Jacobsen JR;Liang K;Shilatifard A;Dowell RD;Old WM;Bentley DL;Taatjes DJ
通讯作者：
Taatjes DJ
DOI：
10.1002/jcsm.12267
发表时间：
2018-04
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Daly LE;Ní Bhuachalla ÉB;Power DG;Cushen SJ;James K;Ryan AM
通讯作者：
Ryan AM
影响因子：
3.7
作者：
Ileana, Terruzzi;Anna, Montesano;Livio, Luzi
通讯作者：
Livio, Luzi
影响因子：
16
作者：
Lu, JR;McKinsey, TA;Olson, EN
通讯作者：
Olson, EN
影响因子：
10.5
作者：
Lazaro, JB;Bailey, PJ;Lassar, AB
通讯作者：
Lassar, AB