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引用次数: 0
摘要
致癌转录激活与肿瘤的发展和化疗或靶向治疗引起的耐药性有关。超延伸复合体(SEC)是后生动物调节基因转录和表达的重要复合体,与生理活动密切相关。在正常的转录调控中,SEC可以触发启动子逃逸,限制转录伸长因子的蛋白水解降解,增加RNA聚合酶II (RNA polymerase II, POL II)的合成,调控人类许多正常基因刺激RNA伸长。在癌症中,SEC的失调伴随着多种转录因子,促进癌基因的快速转录,诱导癌症的发生。在这篇综述中,我们总结了SEC调节正常转录的机制及其在癌症发生中的重要作用的最新进展。我们还重点介绍了SEC复合物靶标相关抑制剂的发现及其在癌症治疗中的潜在应用。
Targeting the super elongation complex for oncogenic transcription driven tumor malignancies: Progress in structure, mechanisms and small molecular inhibitor discovery.
Oncogenic transcription activation is associated with tumor development and resistance derived from chemotherapy or target therapy. The super elongation complex (SEC) is an important complex regulating gene transcription and expression in metazoans closely related to physiological activities. In normal transcriptional regulation, SEC can trigger promoter escape, limit proteolytic degradation of transcription elongation factors and increase the synthesis of RNA polymerase II (POL II), and regulate many normal human genes to stimulate RNA elongation. Dysregulation of SEC accompanied by multiple transcription factors in cancer promotes rapid transcription of oncogenes and induce cancer development. In this review, we summarized recent progress in understanding the mechanisms of SEC in regulating normal transcription, and importantly its roles in cancer development. We also highlighted the discovery of SEC complex target related inhibitors and their potential applications in cancer treatment.
期刊介绍:
Advances in Cancer Research (ACR) has covered a remarkable period of discovery that encompasses the beginning of the revolution in biology.
Advances in Cancer Research (ACR) has covered a remarkable period of discovery that encompasses the beginning of the revolution in biology. The first ACR volume came out in the year that Watson and Crick reported on the central dogma of biology, the DNA double helix. In the first 100 volumes are found many contributions by some of those who helped shape the revolution and who made many of the remarkable discoveries in cancer research that have developed from it.