生物
转座因子
核糖体生物发生
生物发生
DNA转座因子
遗传学
细胞生物学
计算生物学
核糖体
基因组
核糖核酸
基因
作者
Zhenbo Tu,Mahmoud A. Bassal,George W. Bell,Yanzhou Zhang,Yi Hu,Liza M. Quintana,Deeptha Gokul,Daniel G. Tenen,Antoine E. Karnoub
标识
DOI:10.1016/j.molcel.2024.09.025
摘要
Transposable elements (TEs) are indispensable for human development, with critical functions in pluripotency and embryogenesis. TE sequences also contribute to human pathologies, especially cancer, with documented activities as cis/trans transcriptional regulators, as sources of non-coding RNAs, and as mutagens that disrupt tumor suppressors. Despite this knowledge, little is known regarding the involvement of TE-derived genes (TEGs) in tumor pathogenesis. Here, systematic analyses of TEG expression across human cancer reveal a prominent role for pogo TE derived with KRAB domain (POGK). We show that POGK acts as a tumor suppressor in triple-negative breast cancer (TNBC) cells and that it couples with the co-repressor TRIM28 to directly block the transcription of ribosomal genes RPS16 and RPS29, in turn causing widespread inhibition of ribosomal biogenesis. We report that POGK undergoes deactivation by isoform switching in clinical TNBC, altogether revealing its exapted activities in tumor growth control.
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