The 26S proteasome complex: an attractive target for cancer therapy.
The 26S proteasome complex: an attractive target for cancer therapy.
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DOI：
10.1016/j.bbcan.2011.10.003
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发表时间：
2012-01
影响因子：
11.2
通讯作者：
Bhaumik, Sukesh R.
中科院分区：
文献类型：
--
作者：
Frankland-Searby, Sarah;Bhaumik, Sukesh R.
26S蛋白酶体复合物参与多种肿瘤蛋白、转录因子、细胞周期特异性细胞周期蛋白、细胞周期蛋白依赖性激酶抑制剂、鸟氨酸脱羧酶和其他关键调节细胞蛋白的atp依赖性蛋白水解降解。因此，蛋白酶体直接或间接地调节许多重要的细胞过程。这些细胞活动调节的改变与癌症的发展有关。因此，蛋白酶体已成为治疗多种癌症的一个有吸引力的靶点。一些针对26S蛋白酶体复合物蛋白水解活性位点的蛋白酶体抑制剂已经被开发出来并进行了抗肿瘤活性测试。这些蛋白酶体抑制剂通过诱导不同肿瘤类型的细胞凋亡而显示出令人印象深刻的抗肿瘤功能。此外，蛋白酶体抑制剂已被证明可诱导细胞周期阻滞，抑制血管生成、细胞-细胞粘附、细胞迁移、免疫和炎症反应以及DNA修复反应。许多蛋白酶体抑制剂目前正处于治疗多发性骨髓瘤和实体瘤的临床试验中。许多其他具有不同效率的蛋白酶体抑制剂正在开发和测试其抗肿瘤活性。目前在临床试验中的几种蛋白酶体抑制剂与其他药物如组蛋白去乙酰化酶（HDAC）抑制剂、Akt（蛋白激酶B）抑制剂、DNA损伤剂、热休克蛋白90 （Hsp90）抑制剂和来那度胺联合使用时，显示出显著提高的抗肿瘤活性。蛋白酶体抑制剂硼替佐米目前用于临床治疗多发性骨髓瘤和套细胞淋巴瘤。在这里，我们讨论26S蛋白酶体复合物在癌变和不同的蛋白酶体抑制剂及其在治疗多种癌症中的潜在治疗应用。
The 26S proteasome complex engages in an ATP-dependent proteolytic degradation of a variety of oncoproteins, transcription factors, cell cycle specific cyclins, cyclin-dependent kinase inhibitors, ornithine decarboxylase, and other key regulatory cellular proteins. Thus, the proteasome regulates either directly or indirectly many important cellular processes. Altered regulation of these cellular events is linked to the development of cancer. Therefore, the proteasome has become an attractive target for the treatment of numerous cancers. Several proteasome inhibitors that target the proteolytic active sites of the 26S proteasome complex have been developed and tested for anti-tumor activities. These proteasome inhibitors have displayed impressive anti-tumor functions by inducing apoptosis in different tumor types. Further, the proteasome inhibitors have been shown to induce cell cycle arrest, and inhibit angiogenesis, cell-cell adhesion, cell migration, immune and inflammatory responses, and DNA repair response. A number of proteasome inhibitors are now in clinical trials to treat multiple myeloma and solid tumors. Many other proteasome inhibitors with different efficiencies are being developed and tested for anti-tumor activities. Several proteasome inhibitors currently in clinical trials have shown significantly improved anti-tumor activities when combined with other drugs such as histone deacetylase (HDAC) inhibitors, Akt (protein kinase B) inhibitors, DNA damaging agents, Hsp90 (heat shock protein 90) inhibitors, and lenalidomide. The proteasome inhibitor bortezomib is now in the clinic to treat multiple myeloma and mantle cell lymphoma. Here, we discuss the 26S proteasome complex in carcinogenesis and different proteasome inhibitors with their potential therapeutic applications in treatment of numerous cancers.
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DOI：
10.1074/jbc.m109.014092
发表时间：
2010-02-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Armstrong JL;Flockhart R;Veal GJ;Lovat PE;Redfern CP
通讯作者：
Redfern CP
影响因子：
3.8
作者：
Bektas, Nuran;ten Haaf, Anette;Veeck, Juergen;Wild, Peter Johannes;Luescher-Firzlaff, Juliane;Hartmann, Arndt;Knuechel, Ruth;Dahl, Edgar
通讯作者：
Dahl, Edgar
影响因子：
11.4
作者：
Brandeis, M;Hunt, T
通讯作者：
Hunt, T
影响因子：
8
作者：
Baritaki, S.;Chapman, A.;Bonavida, B.
通讯作者：
Bonavida, B.
影响因子：
11.5
作者：
Anderson, Kenneth C.
通讯作者：
Anderson, Kenneth C.