YY1 cooperates with TFEB to regulate autophagy and lysosomal biogenesis in melanoma

YY1 与 TFEB 协同调控黑色素瘤中的自噬和溶酶体生物合成

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作者:Jing Du, Wenyan Ren, Fengping Yao, Hong Wang, Kexin Zhang, Meiying Luo, Yuxue Shang, Douglas O'Connell, Zhuchun Bei, Hongquan Wang, Ran Xiong, Yongfei Yang

Abstract

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.

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