Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, China.
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Mol Carcinog. 2019 Nov;58(11):2149-2160. doi: 10.1002/mc.23105. Epub 2019 Aug 26.
Autophagy is a self-proteolytic process that degrades intracellular material to maintain cellular homeostasis. Transcription factor EB (TFEB) is the master activator that regulates the transcription of genes involved in autophagy and lysosomal biogenesis. However, the cotranscriptional factors of TFEB are rarely identified. Here, we found that Yin Yang 1 (YY1) regulated autophagy and lysosome biogenesis in melanoma cells. YY1 cooperates with TFEB to regulate autophagy through controlling the transcription of autophagy and lysosome biogenesis related genes. Moreover, suppression of YY1 enhanced the antitumor efficiency of vemurafenib both in vitro and in vivo. Collectively, these studies identify YY1 as a novel cotranscription factor of TFEB in regulating autophagy and lysosomal functions and suggest YY1 could be a therapeutic target in cancer treatment.
自噬是一种自我降解过程，可降解细胞内物质以维持细胞内环境稳定。转录因子 EB（TFEB）是调节自噬和溶酶体生物发生相关基因转录的主要激活物。然而，TFEB 的共转录因子很少被鉴定。在这里，我们发现 Yin Yang 1（YY1）在黑色素瘤细胞中调节自噬和溶酶体生物发生。YY1 与 TFEB 合作，通过控制自噬和溶酶体生物发生相关基因的转录来调节自噬。此外，抑制 YY1 增强了维莫非尼在体外和体内的抗肿瘤效果。总之，这些研究鉴定了 YY1 作为调节自噬和溶酶体功能的 TFEB 的新型共转录因子，并表明 YY1 可能是癌症治疗的一个治疗靶点。
