靶向 MYC 驱动型癌症中的 SAGA 和 ATAC 转录共激活复合物。
Targeting the SAGA and ATAC Transcriptional Coactivator Complexes in MYC-Driven Cancers.
机构信息
Departments of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
出版信息
Cancer Res. 2020 May 15;80(10):1905-1911. doi: 10.1158/0008-5472.CAN-19-3652. Epub 2020 Feb 24.
Abstract
Targeting epigenetic regulators, such as histone-modifying enzymes, provides novel strategies for cancer therapy. The GCN5 lysine acetyltransferase (KAT) functions together with MYC both during normal development and in oncogenesis. As transcription factors, MYC family members are difficult to target with small-molecule inhibitors, but the acetyltransferase domain and the bromodomain in GCN5 might provide alternative targets for disruption of MYC-driven functions. GCN5 is part of two distinct multiprotein histone-modifying complexes, SAGA and ATAC. This review summarizes key findings on the roles of SAGA and ATAC in embryo development and in cancer to better understand the functional relationships of these complexes with MYC family members, as well as their future potential as therapeutic targets.
摘要
靶向表观遗传调节因子，如组蛋白修饰酶，为癌症治疗提供了新的策略。GCN5 赖氨酸乙酰转移酶 (KAT) 在正常发育和致癌过程中与 MYC 一起发挥作用。作为转录因子，MYC 家族成员很难用小分子抑制剂靶向，但 GCN5 的乙酰转移酶结构域和溴结构域可能为破坏 MYC 驱动的功能提供替代靶点。GCN5 是两个不同的多蛋白组蛋白修饰复合物 SAGA 和 ATAC 的一部分。本综述总结了 SAGA 和 ATAC 在胚胎发育和癌症中的作用的关键发现，以更好地理解这些复合物与 MYC 家族成员的功能关系，以及它们作为治疗靶点的未来潜力。
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